The authors detected immunoregulatory cells by two-color cytometric analysis in the peripheral blood of 21 patients with multiple myeloma (MM) and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). CD3-CD56+ cells increased in both MGUS and IgG, IgA type MM in clinical stage (CS) I & II, whereas CD3+ cells decreased. On the other hand, the CD4/8 ratio, the proportions of CD45RA+ cells and CD29++ cells in CD4+ cells, and S6F1++ cells in CD8++ cells remained normal. In CS III MM of IgG and IgA type, CD3-CD56+ cells did not increase, although CD3+ cells decreased. Additionally, both CD4/8 and CD4+ CD45RA+/CD4+ ratios were low, while the proportions of CD29++ cells in CD4 cells and S6F1++ cells in CD8++ cells were high. However, this type of change in the T-cell subset balance was not observed in CS III MM of the Bence-Jones type, which showed no significant elevation of serum M-protein. These findings suggest that serum monoclonal idiotypes could affect immunoregulatory cells, especially T cells.