Cytotoxic effector cell responsiveness to host and/or virus-determined hepatocyte surface membrane antigens has been postulated as an important pathogenetic determinant of hepatocellular injury in hepatitis B virus infection. Assuming that such effector cell populations would be detectable in peripheral blood, the present study was designed to examine 2 questions: first, whether target cells that normally express liver-specific protein (LSP) and hepatitis B surface antigen (HBsAg) are selectively destroyed by peripheral blood effector cells from patients with viral hepatitis; second, whether cytotoxic effector cell function emerges coincident with the development of defective suppressor cell activity in the same patients. No evidence of increased HBsAg or LSP specific cytotoxic effector cell activity was found in the peripheral blood natural killer (NK) or T killer cell populations of patients with acute or chronic viral hepatitis.