Some patients with insulin resistant diabetes have antibodies which bind to and block their insulin receptors. In the past year, we have observed dramatic changes in the clinical and biochemical status of these patients. In two patients, improvement in their insulin resistant diabetes was accompanied by lowering in their titer of anti-receptor antibody and increased insulin binding to their cells. In one patient, insulin receptors underwent proliferation, and hypoglycemia developed; the titer of anti-receptor antibody did not change. In addition to inhibiting insulin binding, these antibodies precipitate soluble insulin receptors prepared from human placenta. Using these anti-receptor antibodies as probes, we have been able to demonstrate that most insulin degradation does not require binding to the receptor. BIBLIOGRAPHIC REFERENCE: Flier, J.S., Kahn, C.R., Jarrett, D.B., and Roth, J.: Characterization of antibodies to the insulin receptor: A cause of insulin resistant diabetes in man. J. Clin. Invest. 58: 1442-1449, 1976.