An apparent problem with increased numbers of nosocomial infections caused by Staphylococcus epidermidis at a large hospital was studied in a clinical-epidemiological investigation. Thirty-six cases of S. epidermidis infection were confirmed on the thoracic surgery, general surgery, nursery and pediatric services during a 3-year period. Nine cases were fatal and six of these occurred in patients following cardiovascular surgery with implanted prothesis. The majority of cases (25/36) occurred following cardiovascular surgery. The median onset of infection was six days from the date of surgery, suggesting infection during the intraoperative period. Although the number of cases studied remains small, two phage types, 71/108/275a/459 and 407-2, did predominate among these clinical infections. Interestingly, during this same time interval these same types predominated among surgical staff members closely associated with these patients. Resistance to antimicrobials was high among isolates tested, with more than 50% of the strains resistant to six or more antimicrobial agents.