Introduction Biochemical and biophysical studies in recent years have demonstrated a steadily widening spectrum of diseases and clinical syndromes related pathogenetically to abnormalities at the molecular level. Such deviations may be hereditary or acquired. Prominent in the latter category are disorders most commonly resulting in "dysproteinemia"—qualitative or quantitative abnormalities of the serum globulin fraction. The clinical significance of the presence of cold-precipitable serum globulins in various disease states has received considerable attention, and improved laboratory methods and increased clinical awareness suggest that such abnormal serum proteins may be present more frequently than previously recognized and may provoke the patient's presenting symptoms. History In 1933, Wintrobe and Buell1 noted that the serum of a 56-year-old patient with multiple myeloma formed a viscid layer when it was cooled to 4 C and a suspension of white material developed which dissolved when the serum was warmed to room temperature. This patient had