We observed the course of cytomegalovirus (CMV) retinitis in 21 eyes of 14 immunosuppressed patients. In two patients, other organisms, specifically Toxoplasma and Candida, also appeared to be causing retinal disease simultaneously. Post-mortem examination was done on 10 eyes from seven patients. At initial presentation, the retinitis was often asymptomatic and diagnosed during routine examination. The ophthalmoscopic picture was characteristic of cytomegalovirus; the early lesion was a small opaque, white granular area of retinal necrosis that spread in a centrifugal, brush-fire-like manner over 1 to 8 months. Vessel sheating and hemorrhages appeared as the disease progressed. In two patients new foci of retinitis developed remote from the original lesion. Four weeks to 4 months (average, 10 weeks) elapsed from the most extensive disease to total resolution. Resolution of active disease left a subtle retinal scar, and final visual acuity was reduced in one half the eyes. Repeated ophthalmoscopic examinations can aid in early diagnosis of CMV retinitis and in ascertaining which persons are most at risk for visual loss.