Cimetidine has been shown to have low acute toxicity in dogs and rodents. Repeated-dose studies of up to 24 months' duration in rodents at doses up to 950 mg day-1 kg-1 showed few adverse effects. Liver weight was consistently increased at the highest dose and testis, prostate and seminal vesicle weights were reduced in a dose- and time-related fashion. Cimetidine was not carcinogenic in the rat. In tests of up to 1 year's duration in dogs two animals receiving 504 mg day-1 kg-1 had to be killed before the end of the study. They had degenerative changes in the liver and renal tubular nephrosis. These and other dogs at 504 mg day-1 kg-1 had elevated serum transaminases. No such changes were seen at 366 mg day-1 kg-1 or less. Prostate weights were reduced in a dose- and time-related fashion. In a 7-year study in dogs, specifically designed for the purpose, no changes of the stomach mucosa were seen during regular biopsy. Although shown to be a mild anti-androgen, cimetidine produced no significant adverse effects in reproductive studies. The large body of evidence that cimetidine is not a risk for gastric cancer is reviewed. Over 30 million patients have so far been treated with cimetidine and the prediction from the animal studies that it would be an extremely safe therapeutic agent has been borne out in practice.