Cytomegalovirus (CMV) is the most common opportunistic pathogen following renal transplantation and remains a major concern in transplantation centers owing to its high morbidity and impact on renal allografts. Pending more effective antiviral drugs, efforts have been directed toward prevention strategies. We conducted a retrospective analysis to evaluate the efficacy of various prophylactic options used at our institution during the period April 1986 to August 1990. All CMV-negative patients with CMV-negative kidneys (D-R-) received screened, CMV-negative blood products (n = 19). CMV-specific immunoglobulins (CMV Ig) were used in 6 patients at increased risk for primary CMV infection and acyclovir was administered to 21 patients at an initial intravenous dose of 5 mg/kg body weight; then oral doses of 800-3200 mg per day were given according to the patients' estimated creatinine clearance. Thirty-two patients did not receive any CMV prophylactic treatment and served as controls. CMV monitoring of the patients during the first 6 months after transplantation showed an overall infection and disease rate of 81% and 38.1%, respectively, in the acyclovir-treated group. Compared with controls, the incidences of infection and disease were higher in the acyclovir-treated patients, with a significant difference for CMV infection (P = 0.002, generalized Wilcoxon test). Only 1 of the 19 D-R- patients presented with CMV infection. CMV Ig-treated patients tended to have less severe disease without any apparent reduction in infection incidence. Given the high rate of infection in patients at risk, we infer that high-dose acyclovir does not prevent CMV infection in our setting of renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)