Cytomegalovirus (CMV) retinopathy, a relentlessly progressive disease that results in permanent blindness, is the most common opportunistic infection of the eye in patients with the acquired immunodeficiency syndrome. Twenty patients with the acquired immunodeficiency syndrome with CMV retinopathy were treated with a new, experimental, antiviral drug, 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (BW B759U), in dosages ranging from 5.0 to 14.0 mg/kg/d for a ten- to 20-day course. In 19 patients (95%), treatment halted the progression of infection and decreased retinal opacification, hemorrhage, and vasculitis. Vision remained stable in most cases. Six patients received no additional treatment. Fourteen patients received continued treatment with a lower maintenance dosage. Retinal disease reactivated in all patients who did not receive maintenance therapy immediately after initial treatment, indicating persistence of live virus despite drug therapy. Reactivation of disease also developed in four (40%) of ten patients receiving continuous, uninterrupted maintenance therapy for longer than three weeks. Reversible neutropenia, requiring cessation of treatment, developed in five (25%) of 20 patients on initial treatment and five (36%) of 14 patients receiving maintenance therapy. Rhegmatogenous retinal detachment was a late complication in four patients. BW B759U appears to be useful in the management of CMV retinopathy by reducing or delaying visual loss.