Famotidine is a specific, long-acting histamine2-receptor antagonist. It is indicated for the treatment of duodenal ulcer, gastric ulcer, gastroesophageal reflux disease, and Zollinger-Ellison syndrome. Since its introduction for the treatment of acid-related disorders in 1985, an estimated 18.8 million patients worldwide have been treated with famotidine. We present a comprehensive safety profile of oral famotidine, incorporating data from investigational trials, postmarketing studies, and reports of marketed use. The excellent tolerability profile of famotidine observed during investigational trials has remained substantially unchanged during postmarketing experience. Famotidine does not notably bind to cytochrome P-450 or gastric alcohol dehydrogenase and therefore has not been associated with clinically significant drug interactions. It is generally well tolerated in patients with cardiovascular, renal, or hepatic dysfunction or with Zollinger-Ellison syndrome who have tolerated doses up to 800 mg daily.