It is known that immunoglobulins can be processed and that idiotypic peptides are presented on MHC class II molecules to T cells. It has also been demonstrated that T cells can recognize a complex of an Id-peptide/MHC molecule as a tumor-specific antigen on B lymphoma cells. However, plasmacytomas, an important type of B cell malignancies, most often lack class II molecules and are thus expected to be poor targets for Id-specific, CD4+ T cells. Nevertheless, we now demonstrate that cloned, MHC class II restricted T cells, specific for a lambda 2(315) idiotypic peptide, convey protection in vivo (Winn assay) against the class II molecule-negative MOPC315 (alpha, lambda 2(315)) plasmacytoma. T cells can also inhibit the growth of MOPC315 cells in vitro provided that MHC compatible (H-2d) splenocytes and extra lambda 2(315) are added. Based on these data we suggest that the myeloma protein secreted by MOPC315 cells attains such a high local concentration in vivo that it is processed and presented by neighboring host APC to the Id-specific T cells. Such activated T cells secrete lymphokines which may directly affect the growth of MOPC315 cells in the vicinity. Alternatively, lymphokines from activated T cells stimulate local host cells, like macrophages, to become tumoricidal.