During a 22-month period, 47 patients with 49 consecutive episodes of Staphylococcus aureus bacteremia were identified and observed prospectively for the development of endocarditis and metastatic infection. Eighteen (37%) of the episodes were community-acquired and 31 (63%) were nosocomial. The mean patient age was 55 years, and all but nine patients had one or more underlying diseases. A primary focus was identified for 38 episodes (78%) most often an intravenous catheter, and 21 episodes (43%) were associated with a removable focus of infection. In this group, no patient had endocarditis after a mean duration of 20 days of therapy. Overall, two of 47 patients had endocarditis by clinical criteria; one was a drug abuser and one had no known heart disease. Forty-five of 49 episodes were treated with a single antimicrobial agent. There were 12 (24%) deaths in this series, seven (14.2%) directly due to staphylococcal infection. In this prospective study we found a low but definite risk of endocarditis associated with S aureus bacteremia. The mortality was similar to that in other recently published studies. All deaths occurred within two weeks of initiating therapy, indicating the potential importance of host factors in the outcome.