The effect of coculturing nonadherent and plastic adherent cells from the spleen with MOPC 104E KI81 for short (24 h) and long terms (7 days) was investigated. In both culture systems, the effect of the spleen cells on the secretion of IgM by plaqueforming cells assay and growth of the plasmacytoma by cell counts and flow cytometry was measured. In these studies, a low effector target (E:T) ratio which did not produce cytotoxicity to MOPC 104E cells was used. We observed that while nonadherent spleen cells from normal or MOPC 104E-primed mice inhibited secretion of IgM by the MOPC 104E cells, they stimulated the proliferation of MOPC 104E cells two times faster than MOPC 104E cells cultured alone. Plastic adherent cells from the spleens of normal mice or MOPC 104E-primed mice also inhibited secretion of IgM by the tumor cells as measured by plaque formation, and stimulated proliferation of MOPC 104E in 24 h coculture. Plastic adherent cells from normal nonprimed mice initially stimulated the myeloma to grow, but by 24 h, a large fraction of the population was in the G1 or possibly resting state. The effect of nonadherent and plastic adherent cells on the stem cell activity of MOPC 104E was also tested in 7-day colony-forming assays. Nonadherent cells had no effect on colony-forming units or plaque formation. Plastic adherent cells from normal spleen cells inhibited plaque formation by 68% but had no effect on colony formation. However, plastic adherent cells from spleens of mice primed in vivo with MOPC 104E tumor cells suppressed plaque formation by 98% and also reduced colony formation. The results showed that inhibition by macrophages of IgM production by MOPC 104E cells is independent of cell proliferation. The adherent macrophages from both normal and in vivo-primed spleen cells were Mac. 1 positive after 7 days of coculture with MOPC 104E cells. However, the density of Mac. 1 was greater on primed macrophages. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.