Beta cell hypersecretion is associated with the syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans. It is unknown whether concomitant alpha cell secretory dysfunction occurs in patients with this syndrome. The authors evaluated the gastroenteropancreatic hormones in four family members with varying degrees of the hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome. Gastroenteropancreatic hormones were measured during oral glucose tolerance test with and without subcutaneous octreotide injection. The study revealed that the administration of subcutaneous octreotide resulted in suppression of beta cell function (insulin and c-peptide) but had no effect or a delayed effect on alpha cell secretion (glucagon). Furthermore, the severity of glucagon abnormalities paralleled that of beta cell hypersecretion and the clinical and phenotypic manifestations of acanthosis nigricans in our four patients. We speculate that this alpha cell aberration could potentially be involved in the altered glucose homeostasis and perhaps the skin manifestations of this syndrome. Therefore, glucagon levels should be evaluated in the hormonal studies in patients with hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome.