The primary immune response to sheep red cells (SRC) in plasmacytoma (PC)-bearing mice is consistently depressed; the degree of depression is dependent on tumor size and the dose of antigen administered. Mice bearing the two PC which most severely depress the primary response also have an impaired ability to mount a secondary response to SRC. The primary response of PC-bearing mice to a thymus-independent antigen is also depressed, indicating that B cells are at least one of the cell populations adversely affected in tumor-bearing hosts. However, the B cell precursors of antibody-forming cells, antigen-binding cells, are found in normal quantities and appear capable of binding antigen. The data also suggest that the PC which cause the most severe immunodepression affect the maturation of the precursors of antibody-forming cells whereas those tumors that have a significant but less marked effect on antibody production do not appear to alter the process of differentiation in antigen-triggered cells.