Conflicting information concerning the acute effect of hyperinsulinemia on circulating adrenal androgens, specifically DHEAS, is available. The effect of PCOD or obesity on this response is unclear. We prospectively examined the acute response of circulating DHEAS to the physiological rise in serum insulin after an OGTT in 10 women with PCOD (5 obese and 5 normal weight) and 10 ovulatory euandrogenic women (5 obese and 5 normal-weight). All underwent a standard 75-g 2-hour OGTT. Insulin and DHEAS were measured before and after OGTT. To control for the potential dilutional effects induced by hyperinsulinemia or hyperglycemia on intravascular tonicity, DHEAS levels were correlated to serum protein. As expected, the 2-hour insulin levels were significantly greater than baseline. No significant changes in circulating DHEAS or in the DHEAS to protein ratio was observed in any patient group 2 hours after glucose-induced hyperinsulinemia. The power of this study was greater than 89% for an alpha error of 0.05 and an expected change in DHEAS of 25%. In summary, it appears unlikely that acute increases in insulin within the physiological range are important in the regulation of circulating DHEAS in either PCOD or euandrogenic women, independent of obesity.