Seventeen patients with the acquired immune deficiency syndrome and cytomegalovirus retinitis were treated with the antiviral drug ganciclovir (9-[1,3-dihydroxy-2-propoxy-methyl]-guanine, DHPG). Eight eyes of five patients developed rhegmatogenous retinal detachment after initiation of treatment. Multiple breaks in areas of peripheral, healed, atrophic retina accounted for the detachments. All seven eyes that underwent surgery had extensive retinal detachments that were reattached with vitrectomy and silicone oil. Retinotomy and retinal tacks were necessary in two cases that were complicated by severe proliferative vitreoretinopathy. In the fellow eye of one patient, laser treatment was used prophylactically to wall off a peripheral patch of healed retinitis. Endoretinal biopsies and culture were taken in five eyes; evidence of persistent cytomegalovirus was seen in two cases despite concurrent and clinically effective antiviral therapy.