In a micrototoxicity assay, lymphocytes from ten out of sixteen patients with HBsAg-negative chronic active hepatitis have been shown to be cytotoxic to autologous hepatocytes isolated from percutaneous liver biopsies. This cytoxicity was demonstrable in all six untreated patients but in only four out of ten receiving immunosuppressive treatment, the presence of cytotoxicity showing a significant association with the activity of the disease assessed histologically. The addition of excess purified lipoprotein (LSP), derrived from the hepatocyte plasma membrane, blocked the reaction in all cytotoxic cases, indicating that LSP was the major target antigen. Enriched fractions of T cells were cytotoxic in only one case, whereas non-T cell fractions were cytotoxic in the other ten cases investigated in this way. For optimum T cell cytotoxicity, effector and target cells must share histocompatibility determinants and the results of this study using an autologous system show conclusively that the lymphocyte cytotoxicity found in HBsAg-negative chronic active hepatitis is mediated by a non-T cell population.