The plasma androgen responses to multiple-dose insulin infusions were determined in six normal females, four normal males, five obese females, and in three females with severe insulin resistance, hirsutism, and acanthosis nigricans. During the insulin infusions, the plasma glucose concentrations were maintained at 85 ± 1 mg/dL by variable infusions of dextrose. Plasma androstenedione was augmented by 27–39% at physiologic insulin concentrations in the normal subjects and the obese group, and by 25% at hyperinsulinemic levels in the insulin-resistant group with acanthosis nigricans. The increased androstenedione concentrations achieved in the normal females and obese females were similar to the hyperandrogenemic levels seen in the acanthotic subjects in the basal state. Plasma cortisol also increased in all groups from 19% in normal females to 135% in obese females during the insulin infusions, but these changes did not reach statistical significance. These studies suggest that hyperinsulinemia may play a pathogenic role in the hyperandrogenemia of polycystic ovarian disease.