The interaction between nafcillin and cyclosporine was examined in lung transplant recipients receiving cyclosporine-based immunosuppression. Nine recipients received nafcillin for one week posttransplant and 10 recipients did not receive nafcillin. Age, sex, pretransplant renal function, type of transplant procedure, use of cardiopulmonary bypass, and initial cyclosporine dose were not significantly different between groups. The degree of renal dysfunction during the early postoperative period was significantly greater in the lung recipients receiving nafcillin. Although cyclosporine doses were significantly higher in the nafcillin group, this was not reflected by differences in cyclosporine levels. No difference in survival or incidence of allograft rejection was seen--however, the incidence of viral infection was significantly higher in the patients who received nafcillin. Based on our findings the use of an alternative antibiotic for antistaphylococcal prophylaxis in transplant recipients receiving cyclosporine is recommended.