Euglycemic insulin clamp studies were performed at a sustained physiological insulin concentration of 420 +/- 35 pmol/L (60 +/- 5 muU/mL) in five women who had undergone bilateral oophorectomy and in five intact normal women during the follicular phase of their menstrual cycles to determine the relative contributions of the ovary and adrenal glands in insulin-related augmentation of androgen secretion. Normal women increased their plasma dehydroepiandrosterone (DHEA) concentration by 7.3 +/- 0.4 nmol/L (to 239% +/- 15% of basal), but in oophorectomized women DHEA increased by 1.4 +/- 0.4 nmol/L (to 135% +/- 15% of basal). Thus, the acute response in DHEA to insulin infusion in women without ovaries was only 20% of that seen in intact women. The androstenedione response in oophorectomized subjects was 27% of that seen in controls. We conclude that the insulin stimulation of androgen production occurs predominately at an ovarian site.