Human sera containing M-proteins were tested for their capacity to bind nitrophenyl haptens. About 1.5% of 580 M-proteins showed significant binding for either DNP-caproate or DNP-lysine. In all active sera, binding was due to the M-protein. By contrast, tests of 319 sera by immunodiffusion against nitrophenyl-protein conjugates resulted in many false positive and false negative reactions, indicating that this is a less satisfactory method for detecting M-proteins with antibody activity.