In order to clarify the relationship between HLA-DR antigen expression in the liver and human HIV infection, we studied 66 non-autopsy specimens obtained from HIV-infected patients with and without AIDS; 33 biopsies from HIV-negative patients were considered for control purposes. All biopsies were immunohistochemically tested with monoclonal antibody TAL-1B5, reacting with the alpha-chain subunit of HLA-DR in the avidin biotin complex method. We found occasional and usually weak HLA-DR expression on hepatocytes and biliocytes. By comparison with controls, HIV-positive cases showed a significantly higher percentage of HLA-DR immunoreactivity on hepatic artery and portal vein endothelial cells. No relationship was demonstrated between HLA-DR endothelial expression and the CD4+ lymphocyte count or grade of portal/periportal inflammation in the liver. The biological significance of HLA-DR expression on intrahepatic vascular endothelial cells in HIV infection still remains to be clarified.