The incidence and clinical relevance of cytomegalovirus (CMV) infection has been investigated in 120 consecutive renal allograft recipients receiving cyclosporin A and low-dose steroid (CsA/LDS) immunosuppression. Forty patients (33.3%) showed serological evidence of recent CMV infection; 21 patients (17%) developed clinically symptomatic infection. A seronegative recipient status and an aggressive additional immunosuppressive therapy were significant risk factors for the development of serological infection. There was, however, no difference with regard to these or any other relevant parameters (HLA matching; pretransplant history) between the symptomatic and asymptomatic group. Furthermore there was no influence of CMV infection, whether symptomatic or not, on graft outcome. During the study CMV infection prophylaxis consisted of single-shot CMV hyperimmunoglobulin in 72 patients immediately before grafting, recombinant interferon alpha 2 in 28 patients, and placebo in 20 patients. There was no beneficial effect of either interferon or hyperimmunoglobulin on the incidence and severity of CMV infection. However, steroid-resistant vascular rejections were much more common in the interferon group. We conclude that the incidence of CMV infection after kidney transplantation using CsA/LDS immunosuppression is lower when compared to kidney grafting with conventional immunosuppression. Prophylactic treatment with single-shot hyperimmunoglobulin is not effective, and recombinant interferon alpha 2 prophylaxis may even exert deleterious effects on graft survival by inducing steroid-resistant vascular rejection.