The present study examines the hypothesis that HIV infection of the choroid plexus (CPx) may be an important site of viral entry into the brain. Formalin-fixed, paraffin-embedded CPx was obtained from 25 patients with AIDS and 13 nonAIDS patients and was processed for light microscopy and for immunohistochemical detection of HIV gp41, T and B lymphocytes, monocytes/macrophages and endothelial cells. Eleven of the 13 nonAIDS CPx were normal and 2 contained inflammatory foci of undetermined etiology. The stroma contained T lymphocytes in all and monocytes in 22%; B lymphocytes and HIV antigen were absent. Choroid plexus of the AIDS cases contained opportunistic infections or lymphoma in 12 and inflammatory foci alone in 6; 7 were normal. T lymphocytes were present in 70% and monocytes in 50%. In addition to the stromal localization, monocytes also were present in supra-epithelial regions and within or adjacent to the capillary endothelium. HIV-positive cells in the CPx were found in 11 cases (44%) and in the supra-epithelial area in another 2. Their presence correlated with neither infection nor lymphoma of the CPx or brain. They were situated in the stroma, supra-epithelial region and (rarely) capillary endothelium. Immunohistochemistry on serial sections identified the HIV-infected cells as monocytes, including those by capillary endothelium and in supra-epithelial areas. The study demonstrates that the CPx contains HIV-infected monocytes in almost half of the cases. Their apposition to endothelium suggests hematogenous origin. These results support the hypothesis that HIV encephalitis may develop from CPx infection.