Immunoglobulin-secreting cells (ISC) in the peripheral blood of healthy individuals and in the bone marrow, peripheral blood, or plasmacytomas of patients with multiple myeloma were enumerated by a protein-A plaque-forming cell assay after treatment with anti-Ia antibody and complement. Rabbit anti-human B-cell antisera and monoclonal anti-Ia antibody (OKIal) were used. By this treatment, the number of ISC in the peripheral blood of healthy individuals decreased to half, and that of M-protein-secreting cells from some patients with multiple myeloma also decreased markedly. In one patient, the number of M-protein-secreting cells in the bone marrow were markedly reduced by this treatment, but this was not the case after 6 months of chemotherapy, suggesting that the chemotherapy reduced chiefly the Ia-positive myeloma cells rather than Ia-negative myeloma cells.