The adaptation to long-term starvation is different in men and women. To evaluate whether there are also sex differences during short-term fasting (< 24 hours), we studied glucose metabolism after 16 and again after 22 hours of starvation in healthy subjects: six men, six women in both the follicular and luteal phases of their menstrual cycle, and six women on oral contraceptives ([OCC] day 12 of cycle). Glucose oxidation was measured by indirect calorimetry, and hepatic glucose output by infusion of 3-3H-glucose. There were no differences in hepatic glucose output between men and women during short-term fasting. The basal (16 hours) plasma glucose concentration was lower in women on OCC than in men (P < .05). Prolongation of the postabsorptive state induced a similar decline in plasma glucose concentrations in all groups. Basal (16 hours) glucose oxidation was lower in women on OCC than in men (P < .05). Prolongation of the postabsorptive state by 6 hours caused a significant decrease in glucose oxidation only in men. After 22 hours of fasting, glucose oxidation was lower in women on OCC than in women with normal menstrual cycles. In conclusion, the metabolic adaptation to the postabsorptive state (< 24 hours of fasting) is regulated differently in women on OCC as compared with women with normal menstrual cycles and men. These differences preclude inclusion of women on OCC in studies of glucose metabolism in the postabsorptive state.