The mixed lymphocyte-autologous tumor cell reaction (MLTR) was performed in 15 patients with hematological malignancies. Lymphocyte proliferative response and generation of cytotoxic cells against autologous tumor cells were evaluated and as was the effect of interferon-beta (IFN-beta) (750 IU/ml). Lymphocytes from patients during complete remission had sufficient functions in mixed lymphocyte culture with normal lymphocytes. Tumor cells stimulated allogeneic lymphocytes, although to a generally lesser extent as compared with remission lymphocytes from the same patients. Increased [3H]TdR uptake was observed in 5 patients and was suppressed by the addition of IFN-beta. Autologous tumor cell kill activity was induced by MLTR in 3 patients; IFN-beta-enhanced killing activity was present in these patients as well as in 3 other patients. Tumor cells from the 3 patients with positive autologous tumor cell kill activity had almost the same stimulating capacity as lymphocytes. The expression of MHC class I antigen and IFN-beta-enhanced expression was observed in all tumor cells studied by indirect immunofluorescence. These data suggest that some factors on tumor cells, in addition to MHC class I antigen, participate in the generation of cytotoxic cells against autologous tumor cells and its enhancement by IFN-beta.