Monoclonal antibodies to antigens on the surfaces of mononuclear cells (MNC) were used to characterize lymphocyte subpopulations infiltrating portal areas and parenchyma of livers in 31 patients with chronic active hepatitis (CAH). The distribution and numbers of infiltrating lymphocytes were determined in serial sections immunostained by the avidin-biotin-peroxidase complex method. T lymphocytes were the major component of inflammatory cells in the portal tracts. In the peripheral blood and portal areas, T helper-inducer (T4+) cells were the more numerous subpopulation. However, the hepatic lobules and areas of "piecemeal" necrosis always contained more T suppressor-cytotoxic (T8+) cells. The latter were demonstrated in contact with HBsAg-containing hepatocytes in tissues of patients with HBsAg-positive CAH. The mean numbers of T lymphocytes infiltrating the portal and periportal areas of livers from patients with HBsAg-negative and HBsAg-positive CAH were not different. Large numbers of B cells forming distinct follicles were seen in tissues from patients with HBsAg-positive CAH. The presence of increased numbers of portal T and B lymphocytes correlated with progressive liver damage as observed in two patients studied at yearly intervals.