Hypoglycemia due to insulin receptor autoantibodies is an extremely rare syndrome; most cases have occurred in women often with a history of autoimmune disease. Almost all of these patients have also had episodes of insulin-resistant diabetes and acanthosis nigricans. Their hypoglycemia may be either fasting or postprandial and is often severe and is attributed to an agonistic action of the antibody on the insulin receptor. Balance between the antagonistic and agonistic effects of the antibodies determines whether insulin-resistant diabetes or hypoglycemia occurs. Hypoglycemia was found to respond to corticosteroid therapy but not to plasmapheresis or immunosuppression.