Milk yield declined significantly between days 22 and 28 of lactation in rats, when lactation was extended by frequent replacement of older litters with younger ones. Corticosterone implants but not cortisol injections or implants prevented this decline. Cortisol, however, appeared to inhibit milk ejection since the mammary glands became engorged with milk and milk yield was improved dramatically by oxytocin injections. In both cases corticosteroid concentrations increased approximately threefold above basal concentrations. Both corticosteroids increased total mammary gland RNA content and lipoprotein lipase (LPL) activity of the mammary gland but were without effect on insulin binding. They also decreased LPL activity, lipogenesis and the number of insulin receptors on adipose tissue. Serum prolactin and insulin concentrations were unaffected by any of the treatments. The results suggest that corticosteroids inhibit milk ejection under certain conditions, may be circulating in lower concentrations, which thereby limit milk production, during prolonged lactation and may improve milk yield during extended lactation in part by suppressing anabolic activity in adipose tissue.