Previous studies have clearly established that murine plasmacytomas suppress B-cell responses, but no effects on T-cell responses have been noted by most investigators. However, in our investigation of the tumor-associated antigens of plasmacytomas, we have found that immunosuppression plays an important role in the complex interaction between host immune T cells and tumor cells. In these investigations, varying the number of plasmacytoma cells added to in vitro induction systems separated two different effects which these cells had on the generation of cytotoxic T cells. On the one hand, when appropriate numbers were present, tumor cells acted as immunogens and stimulated the generation of specific killer cells against tumor-associated antigen or alloantigen which they expressed. In contrast, greater numbers of tumor cells exerted a profound inhibitory effect on the generation of cytotoxic activity when cells inactivated with irradiation were used. Mitomycin-C inactivation of plasmacytoma cells abrogated this inhibitory activity. In further experiments, MPC-II cells that had been inactivated with Mitomycin C were able to prime T cells in vivo, whereas priming by live tumor cells could not be detected in the same situation. It is suggested that immunosuppression by the live tumor cells may account for their inability to prime T cells in vivo. These results indicate that immunosuppression by plasmacytomas may be one of the important variables which influence the generation of cytotoxic T cells against tumor-associated antigens both in vivo and in vitro.