To evaluate more accurately the clinical response of cytomegalovirus retinopathy to ganciclovir, a system for the assessment of disease outcome was developed that uses retinal photographs and three factors: development of new lesions, enlargement of preexisting lesions, and change in retinal opacification of lesion borders. With this system a retrospective comparison was performed of 24 ganciclovir-treated patients and 17 untreated patients with cytomegalovirus retinopathy. A masked assessment showed disease progression in 10 treated patients (43%) during a median period of 22 days. In contrast, 16 untreated patients (94%) had progression of disease during a median period of 25 days. Comparison of treated and untreated eyes also suggests that treatment may prevent deterioration of visual acuity during the same period. This study supports the conclusions of previous uncontrolled studies that ganciclovir is beneficial in the treatment of patients with acquired immunodeficiency syndrome and cytomegalovirus retinopathy. It also demonstrates the utility of the proposed system for assessment of disease outcome that can be used in future studies of therapy for necrotizing viral retinopathies.