Expression of major histocompatibility complex (MHC) class I (HLA-A,B,C) and class II (HLA-DR) antigens was studied in postmortem brain tissue of Alzheimer's disease and age-matched control cases. Monoclonal antibodies to class I antigens stained reactive microglia weakly to moderately and vascular endothelial cells strongly in Alzheimer's gray and white matter. Capillaries were also stained strongly in control brains, but only a few positively stained microglia could be observed in white matter. In Alzheimer cases, HLA-DR positive reactive microglia were more numerous and more strongly staining than MHC class I positive reactive microglia but many cells appeared to express both classes of antigen. Rare large cells of uncertain origin also stained positively for class I. Double immunostaining established that MHC class I positive cells were a separate population from glial fibrillary acidic-protein-positive astrocytes.