Little is known about the natural history of cytomegalovirus (CMV) optic neuritis in the acquired immunodeficiency syndrome. We analyzed the clinical course of CMV optic neuritis in 30 consecutive subjects (35 eyes), and compared the survival of patients with CMV optic neuritis to that of a group having CMV retinitis alone, with both groups matched for ganciclovir therapy. Four untreated eyes had a median final visual acuity of no light perception. The median final visual acuity was 20/100 in treated subjects with a mean follow-up of 6.6 months. Following ganciclovir treatment, 2 eyes showed visual improvement, 17 eyes had unchanged visual acuity, and 12 eyes had marked drop in acuity. Relapse occurred in 4 subjects maintained on single-dose ganciclovir, and was controlled on double-dose ganciclovir. Survival was similar in the group of CMV retinitis alone versus the group of CMV optic neuritis with retinitis. Early recognition and therapy of CMV optic neuritis protects against irreversible visual loss. CMV optic neuritis does not carry a worse prognosis for survival than CMV retinitis alone.