OBJECTIVE To assess the role of intravitreal administration of high doses of ganciclovir as a supplement and alternative to intravenous administration in the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). METHODS A retrospective study of visual outcome, relapse and complications of intravenous and high dose intravitreal administration of ganciclovir alone and in combination. METHODS Twenty-three patients with AIDS and CMV retinitis (37 eyes) were examined by the authors and notes, fundal drawings and photographs reviewed. Initially patients were treated with intravenous ganciclovir alone and given supplementary intravitreal therapy for relapse or vision-threatening retinitis; however, later patients were managed with combination maintenance ganciclovir or maintenance intravitreal treatment alone. RESULTS Relapse and loss of vision occurred frequently in patients treated with intravenous ganciclovir alone or in combination with intermittent intravitreal therapy. Eyes managed with maintenance high dose intravitreal ganciclovir alone or in combination with intravenous treatment did not relapse or lose vision. The most important complication of intravenous administration of ganciclovir was neutropenia (73% of patients), whereas that of intravitreal therapy was endophthalmitis (three eyes). CONCLUSIONS High dose ganciclovir given intravitreally effectively suppressed CMV retinitis and preserved vision without adverse systemic effects or deterioration of quality of life.