We present a case of bilateral herpes simplex and cytomegalovirus retinitis and concurrent encephalitis following acyclovir therapy in a homosexual male with the acquired immune deficiency syndrome (AIDS). At autopsy, herpes simplex virus antigens were readily detected in all retinal layers, retinal pigment epithelium, and choriocapillaris, using an immunoperoxidase technique, whereas herpes simplex antigens in the brain were localized in restricted foci of vascular and subependymal parenchymal cells. Cytomegalovirus antigens were identified in cells in all layers of retina, in retinal pigment epithelium, and in subependymal parenchymal cells in the brain. No cytomegalovirus antigens were detected in any vascular endothelium, in choroid, or anterior to the ora serrata. The widespread expression of herpes simplex virus antigens in this patient's retinas is in marked contrast to the restricted foci of herpes simplex antigens limited to the subependymal region of the brain, and is similar to that seen in murine models of herpes simplex retinitis produced by acyclovir-resistant viral mutants.