Three patients with bacterial endocarditis (one case due to Staphylococcus aureus and two to S epidermidis) failed to improve on standard therapeutic regimens which were judged adequate by in vitro testing for sensitivity. Rifampin was added to the regimen in each case and resulted in increased bactericidal activity in the serum, sterilization of the cardiac valves, and clinical cure. The apparent clinical success that was achieved suggests that further investigation of the effectiveness of therapy with rifampin in selected cases of staphylococcal endocarditis is warranted.