When it comes to cattle, size certainly does matter. But how big is too big? And at what cost?

The beef industry has come to rely on growth-inducing drugs to bulk up cattle before slaughter. But the consequences of using such drugs are a concerning unknown. And in a major move away from one particular growth drug, feedlot operators are refusing to participate in a new, large-scale study of Zilmax, Merck’s branded growth promotant for cattle, NPR reported last month.

Cargill, Tyson, JBS, and National Beef — which together produce more than 80% of the country’s beef — have barred cattle raised with the FDA-approved feed additive, and operators do not want to end up with unsellable livestock.

But instead of abandoning such drugs, several producers are simply using another controversial growth promoting drug instead, called ractopamine.

Since becoming commercially available in the U.S. in 2007, Zilmax helped feedlot operators raise bigger cattle on less food, what is known as improving “feed efficiency.” Used for 20 days before slaughter (plus a three-day withdrawal period), cattle could gain an extra 24 to 33 pounds, netting operators an estimated $15.69 more per heifer and an additional $24.24 per steer, according to a 2011 study published in the Journal of Agricultural and Resource Economics. Despite multiple reports (including from the President of Certified Angus Beef and within the FDA application) that beef from animals raised with Zilmax loses its fatty marbling, and therefore doesn’t taste as good, the drug became a mainstay of the beef industry. In 2012, Merck’s annual sales of the drug in the U.S. and Canada were roughly $160 million.

But in August 2013, citing animal health issues, Tyson — the largest meat processor in the country — announced that it would stop accepting cattle raised with Zilmax by the following month. Nine days later, Merck announced that it would voluntarily withdraw the drug from the market. In December 2013, Reuters uncovered reports that found some cattle fed Zilmax were losing their hooves, rendering them unable to walk. In a March 2014 report from Texas Tech University and Kansas State University looking at a dataset of 722,704 cattle across nine feedlots, researchers found “the incidence of death was 80% greater in animals administered [zilpaterol, the active ingredient in Zilmax] than the comparative control cohort.”

Merck studied the problems Tyson referred to, says David Yates, an Account Director & Technical Consultant with the Food Animal Resource Management Team at Merck, and its scientists found the issues were not attributable to Zilmax but were instead a result of other factors. Yates declined to share what those factors were, and he disputes the findings of the Texas Tech/Kansas State report. “We have about 30-plus studies with over 65,000 head of cattle and, again, we don’t have the mobility issues nor do we have mortality issues,” he says. The studies reported in the drug’s FDA application, approved in 2006, which concluded that “no animal safety concerns were identified,” included 960 cattle.

Beef producers’ decision to stop accepting cattle raised with Zilmax was seen by some as part of a plan to expand into the international markets—including China, Russia, and the EU—that currently ban the drug. “Europe is in violation of their WTO commitments for not following the proper procedure of accepting those international standards. Same with Russia and China,” Yates told Fortune. “It may have more to do with trade than it does with anything else.”

But Zilmax’s exit from the U.S. market did not spell the end of cattle growth drugs. It simply led to renewed interest in the original, less effective growth promotant: Optaflexx, manufactured by Elanco Animal Health, a division of pharmaceutical giant Eli Lilly.

Optaflexx, which became commercially available in January 2004, is the branded name for ractopamine, which, like Zilmax, is a beta-agonist — a a class of medications used in asthmatic humans to relax airway muscles. Beta-agonists were also discovered to be “repartitioning agents,” changing an animals’ metabolism to develop more muscle, which weighs more than fat. Like Zilmax, Optaflexx is banned in China, Russia, and the EU. Commonly used in raising hogs, ractopamine was until recently the minority player in the cattle game because its feed efficiency rate was lower than Zilmax’s — coming in at 14-21% compared to Zilmax’s 28%, according to Beef Magazine. But all that changed when Zilmax was taken off the market. Less than two weeks after Merck stopped selling Zilmax, reports surfaced that Elanco couldn’t keep up with growing demand for Optaflexx. (Elanco told Reuters that it was keeping up with demand.)

It’s unclear how many American cattle receive Optaflexx. The American Meat Institute and the National Cattlemen’s Beef Association both referred Fortune to Elanco, which declined to share those details. Before Zilmax was removed from the market, it was estimated that 70-80% of beef cattle in the U.S. received beta-agonists.

In an email, Tyson representative Gary Mickelson told Fortune, “Our 2013 decision [to stop using Zilmax] did not involve the use of Optaflexx.” Cargill — which was the last of the four major beef producers to accept cattle fed Zilmax — said that the majority of the cattle it processes have been fed Optaflexx or a recently developed generic version of it, and that that number increased when Zilmax was removed from the market. JBS and National Beef did not respond to requests for comment.

Beef from cattle raised with ractopamine is not labeled as such.

Ractopamine use, however, may lead to many of the same problems as Zilmax (except, notably, on the taste issue). In terms of animal welfare, the March 2014 report from Texas Tech and Kansas State examined data on 79,171 cattle from four companies and found that “Cattle administered [ractopamine] were 91% more likely to die than control animals.” An Elanco representative told Fortune that the report “is based on observational information versus rigorous, randomized scientific evaluation … so drawing conclusions from such analysis should be done with caution.”

The original FDA application for Optaflexx, approved in 2003, included results from studies of 1,740 cattle, and found “no indications of concerns for animal safety.” (A 2012 review of FDA records found that when fed to pigs, ractopamine “has resulted in more reports of sickened or dead pigs than any other livestock drug on the market.”)

The health implications for humans who eat beef from Optaflexx-fed cattle have not been closely examined. In the drug approval’s section on human safety, Elanco refers the FDA to the 1999 approval of Paylean, the ractopamine product fed to hogs. But while that approval included tests on rats, beagles, and monkeys, it did not include tests on humans. Elanco says that “human food safety of meat from animals fed Elanco’s ractopamine has been affirmed by 30 regulatory authorities globally using their stringent safety criteria for approval, as well as Codex, the international human food safety standards body.”

However, many nations have banned ractopamine, including China, Russia, and member nations of the EU. Questions about the drug’s safety for humans have arisen in the U.S. as well. In October 2013, the Animal Legal Defense Fund and the Center for Food Safety sued the FDA claiming that the regulator failed to provide the groups with public records on the effects of ractopamine. The international Codex standard, notes CFS, is based on a study that “examined the effects of ractopamine on six young, healthy men, one of whom dropped out after experiencing adverse health effects.” The European Food Safety Authority found that the six-person study “was originally designed as a preliminary” effort. It noted the lack of a double-blind study to avoid placebo effects, that it was “handicapped by the poor statistical power,” and that “significant populations which may be at higher risk for adverse events” were not considered.

Optaflexx has also received FDA approval for combinations with other pharmaceuticals, including one called Heifermax 500. None of these subsequent approvals included human studies. While cattle fed Zilmax go through a three-day withdrawal period before slaughter, to decrease the drug residue left in their bodies before they become meat, instructions for Optaflexx do not include any withdrawal period.

“These drugs could accumulate and generate significant adverse events and drug interactions [in humans] and they could certainly have other pharmacological and physiological effects, short term and long term, which are completely unknown,” says David Gortler, a former FDA Medical Officer and drug safety expert at FormerFDA.com. According to Elanco, the safety studies “support the zero-day withdrawal classification.”

Not everyone is convinced that the industry needs to rely on growth-inducing drugs with increasingly unclear safety records. “Everything about how we feed cattle is better today,” says John Nalivka, president of agriculture advisory firm Sterling Solutions. As a Cargill executive wrote in 2009, thanks to improvements in breeding, health programs, and nutrition, cattle have been getting bigger since the 1970s—long before feedlot owners used beta-agonists. They can continue to get bigger without them, too. According to Nalivka, “It’s not a necessity, it’s an industry habit.”