To evaluate the efficacy and safety of high-dose intravenous acyclovir combined with oral zidovudine as suppressive therapy for cytomegalovirus retinitis in patients with AIDS, a single-arm, outpatient, open-label, phase II pilot study was performed. Between July 1989 and July 1990, 12 men with AIDS, cytomegalovirus retinitis, and salvageable vision received intravenous acyclovir, 10 mg/kg of body weight every 8 h, and oral zidovudine after successful induction therapy with intravenous ganciclovir, 5 mg/kg every 12 h for 14 days. Patients were evaluated weekly. Ten of 12 patients were followed to the time of retinitis progression; two were withdrawn from the study because of concomitant life-threatening infection. The median duration of acyclovir and zidovudine therapy before retinitis progression occurred was 32 days. None of the eight uninvolved eyes in the 10 evaluatable patients developed cytomegalovirus retinitis during study participation. These data suggest that high-dose intravenous acyclovir with zidovudine provides some benefit in suppressing cytomegalovirus retinitis.