The clinical course and the outcome of treatment were studied in 40 patients with primary cytomegalovirus (CMV) retinitis in 57 eyes. All had received one 14-day course of intravenous ganciclovir and all were free of other end-organ CMV disease. All afficted eyes received weekly intravitreal injections of 400 micrograms of ganciclovir for maintenance therapy. Median survival of patients was at least 13 months. Fifteen patients had 19 new opportunistic infections during the observation period, but none developed new nonocular CMV disease. Active retinitis recurred in 68.4% of the eyes while receiving maintenance therapy, with a median time to progression of 14.7 weeks. CMV retinitis occurred in 30.4% of the previously uninvolved eyes (follow-up, 3.1 years). Bacterial endophthalmitis complicated treatment in 1 eye, and 5 eyes developed a retinal detachment. Thus, the long-term treatment of CMV retinitis with weekly intraocular injections of ganciclovir was associated with survival and ocular outcome similar to those reported with systemic ganciclovir.