The autologous mixed lymphocyte reaction (AMLR) and the killer activity generated in the AMLR (AMLR-killer) in the spleen and the peripheral blood of patients with gastric cancer were investigated. The AMLR in cancer patients was suppressed, especially in the spleen, compared to that seen in controls. There was no correlation between AMLR activity and the stage status of the cancer. The cytotoxic activity of AMLRkiller cells against various tumor-cell lines was also suppressed in the spleen, and had a tendency to be suppressed in the peripheral blood of cancer patients. The autologous tumorkilling activity of AMLR-killer cells was developed in cancer patients with high AMLR activity, but was not induced in patients with low AMLR activity. Autoturnor killing activity was decreased by the elimination of CD4' cells, whereas the elimination of CD16' cells resulted in a marked reduction in cytotoxicity against K562, indicating that the non-specific killer cells which lysed K562 were different from the specific killer cells that lysed autoturnor cells. This suggests that AMLR activity is related to the differentiation and proliferation of lymphocytes with specific or non-specific cytotoxic activity and that this activity plays an important role in immune surveillance against tumors.