The paraproteins frequently cause major symptoms in patients with plasma cell dyscrasias. This may be due to their quantity in the circulation, to some unusual physicochemical property, or to a biological effect resulting in interaction with other serum proteins. Detection of antibody-combining activity in myeloma proteins has led to important new information on combining-site structure and the kinetics of antigen-antibody-combining activity. Some antibody-combining specificities seem to be present in a higher than expected frequency. As yet, no major therapeutic advances have followed this more precise characterization of the paraprotein, though some interesting possibilities have been explored in animal models.