To assess tissue sensitivity to insulin during the follicular and luteal phases of the menstrual cycle, two-step euglycemic, hyperinsulinemic clamp studies in combination with tritiated glucose infusion and indirect calorimetry were performed in regularly menstruating women in randomized order. There was no difference in the basal follicular and luteal phase levels of glucose, insulin or glucose turnover. A low-dose (0.25 mU/kg/min) insulin infusion suppressed endogenous hepatic glucose production. There was no difference in tissue insulin sensitivity during a high-dose insulin infusion (1.0 mU/kg/min). Nonoxidative glucose disposal also was similar in the basal and insulin infusion periods. Under euglycemic, hyperinsulinemic conditions, there is no difference in tissue sensitivity to insulin, and intracellular pathways of glucose disposal are not altered by the stage of the menstrual cycle.