The salivary gland inflammatory lesions and renal vasculitic lesions of autoimmune MRL/lpr mice were analyzed for the presence of activated lymphocytes. Immunohistologic analysis revealed that the majority of lymphocyte-like cells in salivary glands and kidneys expressed CD4 antigen (greater than 50%). Lesser numbers of interleukin-2 receptor (IL-2R) expressing and interferon-gamma (IFN-gamma)-producing cells were present (1-5%). CD4+, IL-2R+, and IFN-gamma + mononuclear cells were found in small inflammatory foci. In larger inflammatory foci the IFN-gamma-producing cells were detected in the periphery in comparable numbers as the IL-2R expressing cells although with different location. Large numbers of cells in the inflammatory foci also expressed MHC Class II molecules (greater than 50%). The expression of IL-2R and production of IFN-gamma in the tissue lesions indicate presence of activated inflammatory T cells. Production of IFN-gamma by the infiltrating mononuclear cells may induce Class II antigens on epithelial cells and stimulate further T cell migration into the inflammatory site.