Studies on the sera and isolated proteins from 14 patients with gammaG3 multiple myeloma revealed a concentration- and temperature-dependent aggregation which was not encountered in 26 sera from patients with multiple myeloma involving other gammaG subgroups. When the gammaG3 myeloma sera were diluted and characterized by analytical ultracentrifugation, complex formation was minimal. However, when these sera were examined undiluted, marked complex formation was observed. Studies on the isolated proteins, their enzymatic fragments, as well as their heavy and light polypeptide chains localized the aggregating sites to the Fd fragment of the heavy chains. The findings were also documented by acrylamide-gel electrophoresis and capillary tube viscometry.THE HYPERVISCOSITY SYNDROME WAS OBSERVED IN SIX PATIENTS: three with gammaG3 myeloma and three with gammaG1 myeloma. In the latter group extreme protein concentrations appeared essential for the development of the clinical symptoms. The gammaG3 cases, however, because of the aggregation phenomenon, showed the syndrome at relatively low protein concentrations.