Clinical features of 99 patients with staphylococcal infection were reviewed, and sera were tested by solid-phase radioimmunoassay and gel diffusion for staphylococcal antibodies to ascertain whether these variables predict the extent of infection and the need for prolonged therapy. Clinical features, including the presence of a primary site of infection or a continuous pattern of bacteremia, were not sufficient for differentiating endocarditis or complicated bacteremia from uncomplicated bacteremia. Patients with uncomplicated bacteremia were cured by 3 weeks of antibiotic therapy. Positive serologic tests for staphylococcal antibody helped distinguish patients with endocarditis or complicated bacteremia from patients with uncomplicated bacteremia. Radioimmunoassay was more sensitive than gel diffusion for identifying patients with complicated bacteremia. Our results indicate that patients with a positive antibody result 14 days after the onset of infection should be considered to have endocarditis or complicated bacteremia, but a negative antibody result would support short-term antibiotic therapy.