Inordinately high levels of serum immunoreactive insulin in monoclonal immunoglobulinemia (on the problem of "big, big insulin").

1. A patient with occasional attacks of hypoglycemia had levels of serum immunoreactive insulin persistently fifty to one-hundred times the normal value. Immunoelectrophoresis revealed presence of monoclonal IgG in his serum. The patient's diagnosis was established as paraproteinemic lymphoid and plasmocytic reticulosis proximate to multiple myeloma; insuloma was not found. 2. On gel filtration of native serum, only part of the total immunoreactivity was found in the elution position of crystalline insulin; the major part emerged in the early fractions together with the large proteins. After acidification of the serum, however, practically the entire immunoreactivity was recovered in ethanol extracts and proved to be "little insulin" on gel filtration. Only, "little insulin" was also detected after gel filtration of serum incubated with urea. 3. It is suggested that the large component with insulin immunoreactivity obtained in gel filtration of native serum is an insulin-protein complex. The nature of the presumed complex is not clear. It is not a complex of the antigen-antibody type. Insulin "trapping" by monoclonal gamma globulin is considered.