Eight patients with serious staphylococcal infections such as endocarditis, meningitis, epidural abscess, shunt and graft infections were treated with nafcillin, cephalothin or vancomycin in combination with rifampin. In vitro antibiotic sensitivities demonstrated that the Staphylococcus aureus and Staphylococcus epidermidis were highly sensitive to rifampin with minimum inhibitory and bactericidal levels of .0078-.25 micrograms/ml. In all patients reviewed and reported, when serum bactericidal levels were measured before and after the addition of rifampin, there was a positive correlation between microbiological and clinical outcome. Thus, in selected patients with life-threatening infections caused by S. aureus and S. epidermidis rifampin should be considered an adjunctive therapy.