A total of 314 immunocompromised patients with serious cytomegalovirus (CMV) infection treated with ganciclovir administered intravenously were studied. Rates of favorable clinical response among evaluatable patients were 91 (84%) of 108 for CMV retinitis, 35 (83%) of 42 for gastrointestinal CMV infection, and 26 (72%) of 36 for CMV pneumonia. Of 167 treated patients who had AIDS, improvement or stabilization of CMV disease occurred in 83% as compared with 13% of 39 untreated, historical control patients with AIDS and similar CMV disease (P≤.004). Virologic response was noted in 111 (92%) of 121 patients who had sequential cultures of blood, urine, or throat washings for CMY. In an attempt to prevent relapse of CMV disease after discontinuation of ganciclovir, maintenance treatment was evaluated in a group of 61 patients with AIDS and CMV retinitis who had received an initial dosage of ≥7.5 mg/(kg·d) for ≥10 days. Median time to relapse of retinitis was 47 days in patients not receiving maintenance treatment as compared with 105 days in patients treated with 25–35 mg/(kg·w) (P = .0002). Adverse effects of treatment included neutropenia (42%), thrombocytopenia (19%), central nervous system effects (18%), nausea (6%), fever (6%), rash (6%), vomiting, diarrhea, infusion site reactions, and anemia (4% each). It was concluded that ganciclovir has clinical efficacy against CMV disease, as well as an in vivo antiviral effect, and that this agent reduces morbidity of serious CMV infections in immunocompromised patients.