In a double-blind, controlled study 35 herpes simplex virus (HSV) antibody-positive patients were randomized to receive oral acyclovir 200 mg X 4 daily or placebo for 28 days following renal transplantation. The incidence of herpes virus infection was compared in both groups by weekly virus demonstration/isolation testing from throat swabs and urine, and by serum antibody demonstration. None of the 18 patients allocated to acyclovir showed any signs of HSV or varicella zoster virus (VZV) infection during the trial period, whereas 9 of 17 receiving placebo had signs of HSV (P less than 0.001) and 2 of VZV (P less than 0.05) infection. Because of systemic as well as local symptoms of infection in five of the placebo patients, the trial was interrupted and treatment with oral acyclovir instituted. All of them responded well with rapid disappearance of all symptoms. Cytomegalovirus (CMV) was isolated from the urine of two patients in both groups during the trial period; a significant antibody rise was seen later in three of them. There was no evidence of drug-related toxicity during the study.