Antimicrobial prophylaxis of bacterial endocarditis is widely recommended for patients with mitral valve prolapse who undergo procedures that may cause bacteremia. The benefits and risks of this practice have been analyzed on the basis of published data and response to a questionnaire survey of leading authorities on bacterial endocarditis. Among 10 million patients with mitral valve prolapse undergoing a dental procedure, an estimated 47 nonfatal cases and two fatal cases of bacterial endocarditis would occur if no prophylaxis were given, five cases of bacterial endocarditis and 175 deaths due to drug reactions would occur if all patients were given prophylaxis with a penicillin, and 12 nonfatal cases and one fatal case of bacterial endocarditis would be expected if a policy of prophylaxis with erythromycin were adopted. Even using assumptions most favorable to the penicillin regimen, this analysis predicts that no prophylaxis and penicillin prophylaxis would result in a similar number of deaths. No prophylaxis or prophylaxis with erythromycin appears preferable to prophylaxis with a penicillin.