Herpes simplex virus (HSV) and cytomegalovirus (CMV) infections occur frequently after renal transplantation. To determine the effect of these infections on long-term prognosis, we reviewed the charts of 558 patients who underwent primary renal transplantation between Jan 1, 1974 and Dec 31, 1978, at the University of Minnesota Hospitals, Minneapolis, for cultural evidence of these infections. The presence of HSV alone appeared to have a minimal effect on either patient or allograft survival. Positive CMV cultures were associated with decreased patient and allograft survival. Patients with HSV and CMV infections had further reduced patient and allograft survival. Lethal CMV syndrome and associated severe bacterial and fungal infections were common and frequently were the immediate cause of death in patients who had concomitant positive HSV and CMV cultures. Concurrent HSV and CMV infections in renal transplant patients may be a grave prognostic indicator, being associated with enhanced mortality and renal allograft loss.