Drug-drug interactions of cimetidine and possible mechanisms of interaction are discussed. Cimetidine has several actions in vivo that may result in drug-drug interactions. By decreasing acid secretion into the stomach, cimetidine increases the pH of the gastric contents. This may lead to decreased absorption of drugs that require a lower pH for dissolution, or increased absorption of drugs whose absorption is normally decreased by acid inactivation in the stomach. Cimetidine also reduces hepatic blood flow significantly and inhibits microsomal metabolism of drugs inactivated by this system. Both of these actions impair inactivation of numerous drugs. Cimetidine's increase of gastric pH has not been shown to result in clinically important drug-drug interactions. Cimetidine's effects of hepatic metabolism and blood flow are clinically relevant, and several interactions are attributable to them.