Should safety concerns with available ulcer treatment influence drug selection? With the identification of the parietal cell receptors for gastric acid secretion coupled with the introduction of cimetidine in 1977, treatment of acid-peptic diseases was transformed from empiric therapy to an approach based on a clearer understanding of human physiology. Today, physicians are confronted with an array of antiulcer agents that differ within their drug class (e.g., the H2-receptor antagonists) as well as in their mechanisms of action (e.g., neutralize acid, alter mucosal defensive factors, or suppress acid secretion). With minor exceptions, the clinical efficacy of the available antiulcer drugs can be regarded as comparable. Thus, the safety profile becomes the next consideration when choosing among similarly effective drug products. Of the available antiulcer agents, the H2-receptor antagonists as a class have an excellent safety profile, as indicated by more than 25 years of cumulative clinical experience and postmarketing surveillance. Important safety issues with currently available antiulcer drugs, i.e., H2-receptor antagonists, sucralfate, prostaglandin E analogues, and the newest antiulcer agent, omeprazole, are reviewed to place them into perspective for the clinician. 