The pathology of AIDS encephalopathy and its relation to other CNS infections in AIDS was studied in 112 autopsies of AIDS patients and 14 of HIV-positive patients. Special interest was focused on gliomesenchymal nodules (GMNs), a common finding in encephalitis of various etiologies, and on giant cells. GMNs and giant cells were found in 40 patients. These 40 were used for the present study, they were further divided into five groups: I. 21 with AIDS encephalopathy; II. 3 with HIV infection but no AIDS; III. 8 with Toxoplasma encephalitis; IV. 7 with cytomegalovirus encephalitis; and V. 1 with cryptococcus encephalitis. Comparison of the morphological features of GMNs between the five groups revealed parameters which may help distinguish GMNs in HIV infection from opportunistic infections. Small GMN size, low cellular density, ill-defined demarcation from the adjacent brain paraenchyma, minimal tissue rarefaction in the area of GMNs and a strong predilection for the superficial and deep white matter were typical of AIDS encephalopathy. In contrast, opportunistic infections were usually associated with clear demarcation from surrounding brain tissue, high cellular density, strong tissue rarefaction and a predilection for gray matter. Rod cells and macrophages in great numbers were also more commonly found in the AIDS and HIV groups.