In a high proportion of cases blood lymphocytes from cancer patients cultured with autologous tumor biopsy cells undergo blastogenesis. In addition, cytotoxicity against autologous tumor cells is generated. These autoactivated lymphocytes also kill the highly NK-sensitive K-562 and Molt-4 cells. Addition of interferon (IF) at the initiation of the cultures inhibited blastogenesis and the generation of autologous cytotoxicity. On the other hand, lymphocytes already activated for autologous killing in the mixed cultures were not affected by short-term IF treatment prior to the cytotoxic assay. Lymphocytes cultured alone lose their cycotoxicity against K-562. However, when IF was present in these cultures the lymphocytes were cytotoxic for K-562. In addition, lymphocytes cultured for 6 days under conditions which did not result in activation killing of Molt-4 cells could be induced by short-term incubation of the effectors with IF.