The safety and efficacy of intravitreously administered ganciclovir sodium as sole treatment for cytomegalovirus retinitis complicating the acquired immunodeficiency syndrome was studied prospectively in seven patients. All but one of the patients had bilateral cytomegalovirus retinitis and none were able to tolerate therapy with systemically administered ganciclovir because of myelosuppression in six patients and hepatotoxicity in one patient. Intravitreal ganciclovir therapy was discontinued in two patients within the initial 2-week induction phase because of severe intractable thrombocytopenia in one patient and retinal detachment in the other. The retinal detachment could not be conclusively attributed to the injections and was probably a secondary complication of cytomegalovirus retinitis. The remaining five patients were treated weekly, with the course of therapy ranging from a minimum of 14 weeks (18 injections) to a maximum of 56 weeks (58 injections). The patients were followed up for an average of 23.5 weeks. All eyes responded to intravitreal therapy initially, while the six untreated control eyes with cytomegalovirus retinitis all demonstrated progression of disease. Two eyes relapsed while receiving intravitreal doses of 200 micrograms of ganciclovir sodium and were subsequently treated with 300 micrograms of ganciclovir sodium per injection. One eye responded to this regimen, while in the other one the disease progressed. In the long-term treatment group, one eye developed Staphylococcus epidermidis endophthalmitis, which was treated with vitrectomy and intravitreal and systemic antibiotics.