When infused into the third ventricle of rats, insulin dose-dependently reduces food intake and body weight, with doses of 1 mU/day and lower being ineffective. Because corticosterone functionally antagonizes many of insulin's peripheral actions, and because corticosterone acts in the brain to enable hyperphagia under some conditions, a subthreshold dose of insulin (1 mU/day), or its saline vehicle, was infused into the third ventricle of adrenalectomized (ADX) and sham-ADX male Long-Evans rats. Sham-ADX rats that received insulin or saline had no significant change of food intake or body weight over a 2-week interval. Likewise, saline-infused ADX were unaffected. In contrast, ADX rats receiving insulin had a significant reduction of food intake and body weight. These results suggest that the absence of circulating glucocorticoids increases the brain's sensitivity to insulin, and that insulin in the brain acts to lower food intake and body weight via a glucocorticoid-sensitive mechanism.