Sera from 249 patients with monoclonal gammopathies (85 multiple myeloma, 92 benign monoclonal gammopathies, 53 cryoglobulinemia, 19 Waldenström's macroglobulinemia) were examined for the presence of anti-histone activity. Thirty-four sera were found positive. In 12 of these cases the serum monoclonal immunoglobulins were purified and in all, the anti-histone activity appeared to reside in the monoclonal component. None of the patients had symptomatology of lupus despite high titers of anti-histone activity. This study demonstrates an anti-histone activity of monoclonal components of patients with monoclonal gammopathies.