We treated five patients with persistent Staphylococcus aureus bacteremia and endocarditis. Surgical intervention or a "secondline" antistaphylococcal agent was required for bacteriologic cure in each. Special bacteriologic evaluation failed to demonstrate methicillin resistance or antibiotic "tolerance" among the strains of Staphylococcus tested. Cephalosporin agents were noted to be more susceptible to inoculum effect than either methicillin or nafcillin. All patients survived; the explanation for their atypical course is obscure. We present an approach to patients with persistent Staph. aureus bacteremia and endocarditis. © 1978.