The lymphocyte subsets in the peripheral blood and liver biopsy material of 25 patients with HBe antigen-positive type B chronic hepatitis were studied by an indirect immunoperoxidase-labeled antibody method using monoclonal antibodies to surface antigens on pan T cells (Leu-1+), cytotoxic/suppressor T cells (Leu-2a+), helper/inducer T cells (Leu-3a+), natural killer/killer cells (Leu-7+) and B cells (Leu-10+). The percentage of circulating cytotoxic/suppressor cells decreased during acute exacerbation of chronic hepatitis B. In contrast, the percentage of intrahepatic cytotoxic/suppressor cells increased during acute exacerbation. In the liver biopsy specimens taken during acute exacerbation, numerous lymphocytes infiltrated into sites of hepatocytic necrosis, and the majority of these cells had a cytotoxic/suppressor phenotype (Leu-2a+). These findings suggest that T cell cytotoxicity plays an important role in the mechanism of liver cell damage during exacerbations of chronic hepatitis B. The lymphocyte subsets in the blood and in the liver biopsy material of 4 patients with chronic hepatitis B obtained about 2-7 weeks before and after treatment with Ara-A were studied in the same way. In both the peripheral blood and liver, the percentage of cytotoxic/suppressor cells was decreased after the treatment. Most of the patients showed a decrease in serum HBV-associated DNA polymerase activity and HBV antigens (HBsAg and HBcAg) in the liver. These findings suggest that as a result of the reduction of HBV replication due to the anti-viral effect of Ara-A, the T cell cytotoxicity is diminished after treatment with Ara-A.