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The effect on L1210 leukemia in mice of immunostimulation, in combination or not with chemotherapy with either daunorubicin or mitomycin, was studied. Immunostimulation with the immunomodulator P40 isolated from C. granulosum, together with xenogenized syngeneic tumor cells (GA-L1210-Tet: L1210 tumor cells inactivated with glutaraldehyde and coupled with tetanus toxoid), on days -14 and -7 before and days 2 and 9 after tumor inoculation, resulted in significant increase of the mean survival time as compared to control group with or without chemotherapy. Administration of P40 or P40 + GA-L1210-Tet cells, before or before and after inoculation of L1210 cells partly inactivated in vitro with antineoplastic agents, leads to a marked prolongation of mean survival time and to inhibition of ascitic tumor growth in a high percentage of mice. About 50% of the mice treated with P40 + GA-L1210-Tet cells and surviving the first challenge were resistant to rechallenge, providing that P40 + cells were reinjected before the second challenge, whereas all mice treated with P40 alone and surviving the first inoculation, were susceptible to rechallenge. The major conclusion is that treatments of combining chemotherapy, active immunization and nonspecific immunostimulation in the applied sequence are more effective than single treatments for control of L1210 mouse leukemia.