The effect of hydrochloric acid at pH 1.2–3.2 on erythromycin stearate and commercial dosage forms of erythromycin stearate was studied. Under all conditions examined, erythromycin was readily dissolved from the stearate as hydrochloride, and rapidly lost its biological activity in solution. The inclusion of pepsin in the test systems did not affect the results. Although formulation differences somewhat affected the rate of destruction, acid lability was exhibited by all products examined, except enteric-coated tablets. Amounts of acid considered to be normal in the fasting stomach contents of adults during the time likely for a dose to remain in the stomach caused 70–90% destruction within 15 min after the shells started to rupture. Amounts of hydrochloric acid appreciably less than 1 mEq, representing abnormally small quantities even in the fasting state, caused destruction ranging from 30 to 70% of the doses in 15 min. These results are not reconcilable with published statements that the sensitivity of erythromycin to gastric acid is overcome by providing the antibiotic in the form of stearate salt.