To characterize the expression of Ia systemically and locally on mononuclear cells during acute viral encephalitis, weanling mice were inoculated intracerebrally with Sindbis virus (SV), an alphavirus. Peripheral blood mononuclear cells, splenocytes and perivascular inflammatory cells in frozen brain sections were examined immunocytochemically for the presence of Ia. Ia expression increased in the spleen, blood and brain during SV encephalitis. The majority of the cells in the central nervous system (CNS) expressing Ia were perivascular mononuclear cells but Ia was also found on stellate parenchymal cells. Using one micrometer cryopreserved serial sections we identified these parenchymal cells as macrophages and microglia but not astrocytes. We also identified rare Ia-positive cells resembling endothelial cells. Frozen brain sections of SV-infected T cell-deficient nu/nu mice were also examined for Ia expression. The number and percentage of Ia-positive cells in perivascular inflammatory cells were markedly decreased compared to normal mice and Ia-positive stellate parenchymal cells were less numerous. This suggests that immunocompetent T cells are necessary for "normal" infiltration of inflammatory cells and for Ia expression in the CNS during SV encephalitis.