Lymphocytes were propagated with interleukin 2 from liver tissue removed at transplantation from patients with primary biliary cirrhosis or autoimmune chronic active hepatitis. Phenotypic analysis of the cultured lymphocytes as well as the infiltrating cells in situ indicated that the culture technique did not select for a particular phenotype. Eight cultures were tested for cell-mediated lympholysis activity against a bile duct tumor line as well as a hepatocellular carcinoma line, but no specific killing was seen. In addition, no natural killer activity was detected. However, the lymphocyte cultures were able to kill the targets in a lectin-dependent cytotoxicity assay, indicating their cytolytic effector activity. Preliminary studies have demonstrated that lymphocytes extracted from hepatic tissue and hilar lymph nodes from a patient with primary biliary cirrhosis proliferated in response to autologous biliary epithelial cells. These methods might be useful in studying the pathogenesis of primary biliary cirrhosis and other liver diseases with autoimmune features.