The role of ovarian hormones in the long-term control of B-cell function of in the mouse has been examined. Ovariectomised adult female mice were treated with daily subcutaneous replacement doses of oestradiol (5 microgram/kg), progesterone (1 mg/kg), both hormones combined, or vehicle only for 15 weeks. Ovariectomy caused a 40% increase in plasma glucose concentrations during glucose tolerance tests, a 26% decrease in the plasma insulin response to glucose (2 g/kg IP) and a 32% decrease in the plasma insulin response to arginine (2 g/kg IP) compared with control mice. When islets from ovariectomised mice were incubated for 30 minutes in media containing 28 mmol/l glucose or 2.8 mmol/l glucose with 5 mmol/l arginine, insulin release was reduced by 23% and 31% respectively. Total pancreatic and islet insulin content were each decreased by 36%, and the number of B-cells was decreased by 39% in the ovarietomised mice. These detrimental effects of ovariectomy were partially or totally prevented by the oestradiol and progesterone treatments. The results indicate that ovarian oestrogens and progestogens may play an important role in the long-term maintenance of B-cell competence in the female mouse.