Abstract Cytomegalovirus (CMV) infections, either primoinfection or reactivation, remain an important problem in organ transplantation. We therefore designed a prospective study in which pre-transplant CMV-positive renal transplant (RT) patients were randomized to receive for 3 months starting immediately after transplantation either acyclovir or nothing. Between April 1992 and January 1993, 53 cadaveric renal transplantations were performed in our institution. The immunosuppressive regimen included anti-thymo-globulins (ATG), azathioprine, steroids and cyclosporine A. Patients randomized in the acyclovir arm received the drug from day 1 to day 90 (D 90) intravenously as long as the creatinine clearance was not above 10 ml/min and per os afterwards (3200 mg/day if the creatinine clearance was above 50 ml/min). CMV viraemia tests were systematically performed every 2 weeks until day 90 or when febrile episodes occurred. The patients were 53 adults who received a RT during the study period; 37 were included in the study of which 19 received acyclovir prophylaxis (group A) and 18, no prophylaxis (group B). The two groups did not significantly differ according to sex ratio, recipient's age, number of CMV-negative donors and number of days on ATG (10.76 ± 6.16 vs. 8.28 ± 4.21 days). There were significantly fewer viraemia episodes in group A (n= 6) than in group B (n= 13, P < 0.05); nevertheless, the percentage of symptomatic CMV viraemia was the same in both groups (35% vs. 38.5%). The onset of CMV viraemia occurred in the same period in both groups (39 ± 13.8 days vs. 34.3 ± 15 days; P = NS). The number of rejection episodes in the study period was the same in both groups (8 in each). We conclude from this prospective study that post-RT acyclovir prophyfaxis reduces significantly the number of CMV viraemia episodes but does not delay their onset. Furthermore, it has no effect upon the percentage of symptomatic viraemias.