An immunoregulatory factor associated with spleen cells from tumor‐bearing mice was found to potentiate the generation of antibody‐producing cells (APC). In an attempt to characterize the target cell of this enhancing factor (EF), its activity in mice devoid of mature T lymphocytes was tested. Levels of anti‐SRBC APC were augmented when EF was injected together with SRBC to nude mice and “B” mice. In addition, EF potentiated the antibody response against the IgM‐inducing T. independent pneumococcal polysaccharide SIII antigen. These results suggest that EF most probably exerts its enhancing influence directly on B lymphocytes. In a different line of experiments adoptive secondary responses were performed. Mice were immunized with SRBC as carrier or with the NIP‐chicken erythrocytes (as a source of NIP‐specific primed B cells) in the presence or absence of EF. Various combinations of spleen cells from the donor immunized mice were transferred in a mixture with NIP‐SRBC to lethally irradiated recipient mice. EF did not exert any potentiation effect on helper function, except when primed B cells were used. In contrast, a clear activation or clone expansion of hapten‐specific B cells was observed. These findings indicate that the enhancing factor from tumor‐bearing animals directly affected the anti‐genie triggering of B lymphocytes and their subsequent proliferation and differentiation to antibody‐producing cells.