BALB/c mice were given 1 Χ 106MOPC 104E plasmacytoma cells i.v. to disseminate the neoplasm to various organs. Twenty-five days after implantation and at a time when the neoplastic B-cell clone was in the exponential growth phase, the mice were given i.p. injections of a mixture of antigens containing sheep red blood cells and levan. Each mouse was monitored simultaneously for immunoglobulin M (IgM) anti-dex-tran myeloma protein produced by the plasmacytoma and anti-sheep red blood cell hemolysin. The increase and decrease of these markers permit assessment of the expansion of the abnormal B-cell clone during the rise and fall of a normal B-cell clone in response to a specific antigen. The model was used to determine (a) the extent of the suppression of myeloma protein, (b) how long inhibition can be maintained, and (c) how soon it occurs after antigen is administered. The results showed that, as the IgM antibody response to sheep red blood cells begins to peak, it exerts a transient suppressive effect on either the MOPC 104E growth or on the cellular release of MOPC 104E IgM. The suppressive effect was noticeable 4 days after antigen administration for only 24 hr. These results indicated that plasmacytoma cells in vivo can recognize signals for either suppression of growth or release of the idiotypic MOPC 104E IgM and were not inconsistent with the view that myeloma may be the result of a defect in B-cell regulation. © 1981, American Association for Cancer Research. All rights reserved.