Seventeen episodes of persistent Staphylococcus epidermidis bacteremia (one to nine days) occurred in 16 patients with vascular catheters during a 26-month period. Cases were statistically more likely to have a longer hospitalization (54 v 7.6 days, p < .0005), longer duration of antibiotic therapy (22 v 2.5 days, p = .002), presence of a central venous pressure (CVP) catheter (14 v 2, p < 3 × 10-8), and presence of an arterial catheter (4 v 1, p = 0.037) than randomly selected hospitalized patients matched for age, sex, and date of admission. However, when cases were compared with similarly matched non-bacteremic patients having CVP catheters, these characteristics were not significantly different in the two groups. Furthermore, exposure to total parenteral nutrition (TPN) and duration of TPN were not significantly different between cases and controls. Hence, the presence of a CVP catheter appeared to be the major risk factor for 5. epidermidis bacteremia. In 16 episodes, patients had temperature > 38.6°C without another identifiable cause, and the average white cell count for the case group was 19,400/mm. Seven patients also had diaphoresis, confusion, hypotension, or oliguria. Temperatures returned to normal in 13 within 24 hours after catheter removal, and all patients were afebrile and symptom-free within 72 hours. Thus, vascular catheter-associated S. epidermidis bacteremia was an important case of febrile morbidity in these patients.