A longitudinal, prospective study of herpesvirus hominis (HVH, herpes simplex virus) was carried out in immunosuppressed renal allograft recipients using serologic, virologic and clinical techniques. The final study group consisted of 37 patients of which 31 were followed for at least 2 months and 26 for more than 1 year. A 4-fold rise or more in HVH complement-fixing antibody in relation to titers measured at the time of transplantation was found in 11 patients. Eight of these 11 patients had clinically recognizable herpetic lesions. An additional 9 patients had lesions without titer rise being demonstrable. The 20 of the 37 patients studied (54%) had evidence of active infection with HVH. Because of pain and discomfort herpetic sores were of clinical importance in 11 patients and lasted for 1 month or more in 9. Herpetic keratitis was seen in 3 and left permanent damage to sight in 2. Multiple, extensive, prolonged and sometimes destructive herpetic lesions affected 5 (16%) of all patients studied.