SUMMARY1. Intraperitoneal injections of cimetidine into rats markedly reduced gastric acid production. When given at a dose of 50 mg/kg body weight, rate of acid production fell from a mean of 2.73 μmol/min (s.d. = 0.32) to a lowest level of 0.81 (s.d. = 0.28): the difference was highly significant (P<0.005). When given in a dose of 100 mg/kg, the rate of acid production further fell to 0.18 μmmol/min (s.d. = 0.12;P<0.001).2. Treatment with cimetidine in doses of 100 mg/kg 8‐hourly during a 24 h period of restraint prevented the development of acute gastric ulceration in the rat. Pretreatment with cimetidine also protected against the ulcerogenic effects of intragastrically administered bile or lysolecithin.3. The marked sustained reduction of acid production most probably accounts for the protective effect of cimetidine against ulcer production in the rat stom