In seven of eight cases of presumed ocular toxoplasmosis in patients with AIDS, the diagnosis was supported by a reduction or resolution of intraocular inflammation and healing of necrotic retinal lesions after initiation of antiparasitic drug therapy including one or more of the following medications: pyrimethamine, sulfadiazine, clindamycin, tetracycline, or spiramycin. In two cases the diagnosis was confirmed histologically. The cases differed clinically and histopathologically from those in immunocompetent patients. There was no evidence that disease originated in preexisting retinochoroidal scars. Lesions frequently were bilateral and multifocal. Vitreous inflammatory reaction was a common clinical finding, but histopathologic examination demonstrated scant retinal inflammation in areas of necrosis. Ocular toxoplasmosis in these patients with AIDS probably resulted from newly acquired infection or dissemination of organisms from nonocular sites of disease. Infections became clinically inactive with drug therapy in all treated patients, but reactivation and progression of disease occurred when therapy was stopped in two of three patients. Severe retinal necrosis led to retinal tears or detachment in three cases. Ocular lesions were the first manifestation of Toxoplasma gondii infection in four of five patients with evidence of multisystem infection.