Spleen cells of BALB/c mice immunized with purified BALB/c myeloma protein (MP) caused idiotype-specific suppression of DNA synthesis and colony formation by myeloma cells in vitro. Lymphocytes from mice immunized with 315-MP inhibited only MOPC-315 plasmacytoma cells; conversely, lymphocytes from mice immunized with 167-MP inhibited only MOPC-167 plasmacytoma cells. Antisera from those mice that showed cell-mediated inhibition of myeloma growth had no significant effect. The suppressive activity of the spleen cells was markedly reduced by treatment with anti-Thy 1.2 and complement, and the immune cells responsible for the suppression did not adhere to nylon wool. The suppressor cells adsorbed to myeloma protein-coated plates, and after elution, inhibited myeloma cells specifically at a 1:1 effector to target cell ratio. Suppression of myeloma growth was due to cytostatic rather than cytolytic effects. These findings suggest that mice immunized with purified myeloma protein have idiotype-specific T cells that can regulate myeloma cell growth. This mechanism may provide an explanation for the transplantation resistance to myelomas induced by immunization with myeloma protein. Similar idiotype-specific T cells may also play a role in the idiotype-specific regulation of immune responses by acting late in differentiation to block the proliferation of antibody-secreting normal B cells.