To investigate the possibility of human immunodeficiency virus-(HIV) 1 infection of liver cells, liver samples from 17 patients with either acquired immunodeficiency syndrome (AIDS, 13), AIDS-related complex (ARC, 3), or lymphadenopathy syndrome (LAS, 1) were studied. A monoclonal antibody directed against the p24 gag HIV-1 protein was used in an immunoperoxidase assay and yielded positive results in seven out of 17 samples. Staining by anti-p24 antibody was of three types: diffuse in Kupffer cells of most samples, inside granuloma in cells that were probably histiocytes, and in some sinusoidal cells whose origin was difficult to ascertain. Attempts to locate the CD4 membrane antigen showed that it was mainly present on endothelial sinusoidal cells. These results indicate that liver cells, including Kupffer cells, might be infected by HIV-1, and that these cells might be involved in certain liver lesions observed during HIV-1 infection, particularly sinusoidal abnormalities.