The inhibition of pepsin secretion by metiamide and atropine has been studied in the gastric fistula rat and the Heidenhain pouch rat. A comparison of the effectiveness of metiamide and atropine in inhibiting pepsin secretion was made by using doses of the antagonists which produced a similar level of inhibition of acid secretion. In the gastric fistula rat both atropine and metiamide inhibited the basal pepsin output, but atropine was more effective than metiamide in this respect. In the Heidenhain pouch rat a large dose of metiamide which inhibited bethanechol-stimulated acid secretion had no significant effect on the corresponding output of pepsin. In this preparation atropine inhibited both acid and pepsin secretion. Possible reasons for the differences in the two preparations are discussed.