95 of 1,019 (9.3%) sera with monoclonal immunoglobulins (MIg) were found to have cold-reacting lymphocytotoxins (LCT). There was no difference in the prevalence of LCT in multiple myeloma, macroglobulinemia, cancer, lymphoma or benign monoclonal gammopathy. Prevalence of LCT was similar in various classes and types of MIg with the exception of the IgG/λ group in which LCT were more common than in IgG/K (p = 0.013). IgMs had the most potent whereas IgAs had the weakest LCT activity.MIg were purified from 61 LCT-positive sera. 25 pure MIg (41 %) had LCT activity. In the rest, LCT activity resided in other fractions. 64 sera with LCT were tested against B and T cells; 56% were equally cytotoxic to B and T cells, 39% killed more B cells and 5% killed more T cells. 18 purified lymphocytotoxic MIg killed both B and T cells. When serial dilutions of sera, and of purified MIg were tested, in all but one instance the reactivity with the T cells weakened more than that with the B cells. Lymphocytotoxins absorbed to and eluted from the peripheral blood lymphocytes or separately from B or from T cells retained LCT activity against B and T lymphocytes.It may be concluded that about one tenth of sera with M components have lymphocytotoxic activity and that in about 40% of these positive sera, this activity is related to the monoclonal immunoglobulins. LCT react with both B and T cells. Antilymphocyte activity of MIgs may play a role in immunoregulatory abnormalities in plasmalymphocytic diseases.