Histamine2 receptor antagonists are beneficial in treating gastric and duodenal ulcers, gastroesophageal reflux, and hypersecretory states. Histamine2 receptor antagonists are helpful for the prevention of stress ulceration and recurrence of gastric and duodenal ulcer. Four histamine2 blockers are approved for clinical use: cimetidine, famotidine, ranitidine, and nizatidine. This review compares these agents in three areas: efficacy, adverse drug reactions, and drug interactions. Although limited published data exist for famotidine and nizatidine, both are as effective as the better-studied ranitidine and cimetidine when administered appropriately. Subtle differences exist among the four agents in the areas of drug interactions and adverse effects. Individual practitioners may decide if these differences are important enough to affect drug choice.