Immune responses to sheep erythrocytes were enhanced in mice bearing small mastocytomas soon after injection of a few tumor cells. In contrast, mice with larger tumors after transfer of a greater number of mastocytoma cells and those in the later stages of tumor development after transfer of small numbers of tumor cells showed moderately suppressed immune responses. Transfer of spleen cells from mastocytoma-bearing mice to irradiated recipients resulted in more antibody-forming cells as compared to transfer of splenocytes from normal donor mice. The addition of graded numbers of mastocytoma cells to a constant amount of normal spleen cells transferred to irradiated mice also resulted in enhanced responses and increased spleen weights in the recipients. This increase, in direct proportion to the number of mastocytoma cells transferred, also occurred when Escherichia coli lipopolysaccharide (a T-cell independent antigen) was used to immunize animals given spleen cells from normal mice and mastocytoma cells. Mastocytoma cell-free homogenates or X-irradiated tumor cells also heightened immune responses in recipient mice, which indicated that viable cells were not needed for the effect. Such homogenates, as well as the tumor cells per se, stimulated increased lactate dehydrogenase (LDH) activity in the sera of recipient mice. However, tumor cells passaged in tissue culture for several months, those derived from mice bearing a mastocytoma cell line with a low LDH-stimulatory activity, or UV-irradiated mastocytoma cells with a high LDH-stimulatory activity did not induce enhanced plaque-forming cell responses.