This study demonstrated that spleen cells of inbred BALB/c mice with plasmacytomas inhibited proliferation of the B-lymphocyte colony-forming cells that were precursors of immunoglobulin-producing cells. The number of B-lymphocyte colonies/10(5) nucleated spleen cells was depressed in mice with plasmacytomas. The degree of suppression correlated with the size of the tumor. Spleen cells from tumor-bearing mice suppressed the formation of B-lymphocyte colonies by normal BALB/c spleen cells. Treatment of the myeloma spleen cell suspensions with anti-immunoglobulins, anti-theta, or 1,500 rads did not prevent the suppression. Spleen cells from tumor-bearing mice depleted of adherent cells by passage over Sephadex G-10 columns or adherence to plastic dishes did not retain their suppressive activity. Adherent spleen cells inhibited B-lymphocyte colony formation when they were either in direct contact with normal spleen cells or separated from them by a layer of agar. These studies suggested that the immune suppression seen in plasmacytoma-bearing mice occurred partially at the level of the B-lymphocyte progenitor cell and that this suppression was mediated by an adherent mononuclear cell.