The immunoglobulin fractions of serum from patients with spontaneous hyperinsulinaemic hypoglycaemia and others with type 1 diabetes stimulated insulin release both in islet-cell cultures and in vivo in rats. Serum from patients with type 2 diabetes, which is not an autoimmune disease, did not stimulate insulin release. The discovery of islet-cell-stimulating antibodies (ICSTA) completes for the islet the triad of autoantibodies (anticytoplasmic, antiproduct, and antireceptor) previously described in autoimmune thyroid disease. ICSTA may be important modulators of islet-cell secretion in man.