Abstract Premenopausal women become more ketotic than do men during short term starvation. The possible influence of female sex steroids on ketosis during an 84-hr fast was studied in premenopausal women receiving combined oral contraceptive steroids. The results were compared to age and weight-matched women on no steroid birth control regimen. Although concentrations of several plasma substrates, insulin, and glucagon were measured throughout the fast, no differences between groups were observed with the exception of the 36-hr interval. At this time total plasma ketones and betahydroxybutyrate were significantly higher in women receiving oral contraceptives. In a second study six postmenopausal women were investigated in a similar fashion during a 36-hr fast. The procedure was repeated following a 5-day treatment regimen of oral estradiol and medroxyprogesterone acetate. After sex steroid treatment, total plasma ketones and betahydroxybutyrate concentrations exceeded control values significantly at 36 hr while plasma alanine and free fatty acid levels were significantly lower. The results suggest that oral estrogen-progestin combinations increase the ketogenic response of pre- and postmenopausal women during the early phases of total starvation. This hormonal effect may explain, in part, why women are more sensitive to fasting than are men.