Primary tumor cells (MCT) induced in an inbred C3H mouse by 3-methylcholanthrene were fused with 8-azaguanine-resistant L-cells with the use of UV-irradiated HVJ (Sendai virus). Two types of hybrid cell clones showing different behavior in culture were obtained. Both hybrid cell lines expressed H-2k antigen, tumor cell antigen, and L-cell antigen. These hybrid cells failed to produce tumors in normal C3H mice after ip or sc inoculations of as many as 10(6) cells. Normal C3H mice pretreated with the inocula of viable hybrid cells showed specific resistance to the challenge of parental MCT cells. In the Winn test, the effector activity was observed in immune lymphoid spleen cells and was not lost by passage through a nylon fiber column, but was abrogated by treatment with anti-Thy-1,2 antiserum and complement. However, inoculation of these hybrid cells in syngeneic mice bearing MCT cells enhanced tumor growth. In these mice with enhanced tumor growth, generation of cytotoxic T-cells was also observed in the spleen; in sera, however, free cytotoxic antibodies to tumor cell surface antigens and antigen-antibody complexes existed at higher concentrations than in sera of tumor bearers. Sera from mice with tumor enhancement interfered with in vitro cellular cytotoxicity at the level of both target cells and immune spleen cells. Therefore, the inoculation of viable hybrid cells seemed to preferentially stimulate cellular immunity in normal mice but accelerated the humoral response and subsequently enhanced tumor growth in tumor-bearing mice.