Mice bearing TEPC-183, an immunoglobulin M(kappa)-secreting plasmacytoma, exhibit severe suppression of their immune responses to both thymus-dependent and thymus-independent antigens, 2,4-dinitrophenyl, and the type 3 pneumococcal polysaccharide SSS-III. This immunosuppression is not lifted by splenectomy of the tumor-bearing mice or prevented by removal of the spleen prior to tumor injection. On the contrary, splenectomy either before or after tumor implantation further accentuates the immunosuppressed state of tumor bearers and even depresses the immune response of normal mice. A secondary immune response of normal mice 34 to 51 days after splenectomy is still reduced. Thus, spleen cells may play a dual role. While splenectomy may remove a source of suppressor cells in tumor-bearing mice, it also eliminates a major source of antibody-producing cells and results in reduced immune responses of normal and TEPC-183-bearing mice. These findings have clinical relevance since splenectomy is used as a therapeutic and diagnostic procedure in neoplastic lymphoproliferative disorders.