The effect of estradiol, progesterone and norgestrel on serum insulin and glucose levels and on insulin binding to adipocytes, hepatocytes and diaphragm muscle cell membranes has been evaluated in castrated male rats. Estradiol administration (5 micrograms/day X 6) significantly increased basal plasma insulin levels and the amount of insulin bound to fat and liver cells as well as muscle cell membranes. Progesterone treatment (5 mg/day X 6) caused a slight increase of basal insulin levels and a decrease of insulin binding to fat cells. Norgestrel treatment (5 mg/day X 6) decreased both insulin levels and the amount of insulin bound to adipocytes; a much lower dose of norgestrel, 6 micrograms/day X 7, also caused a decline in adipocyte insulin binding due to an apparent increase in the dissociation constant of the high affinity binding sites. These studies demonstrate that ovarian sex steroids have a significant effect on insulin binding to target cells. This animal model would assist in determining the mechanisms involved in changes of carbohydrate metabolism which occur during the menstrual cycle, pregnancy, the menopausal state and with the use of oral contraceptives.