Corticotropin releasing factor (CRF) reduces food intake in rats after central administration. In these studies we examined whether the adrenal gland and the vagus were involved in CRF suppression of intake. One hour intake was reduced by a 5 micrograms (ICV) injection of CRF in sham but not adrenalectomized rats maintained on 0.9% NaCl. In a separate experiment on rats maintained on tap water, the inhibitory effect of CRF (5 micrograms) lasted at least 4 hours in sham rats whereas adrenalectomized rats did not significantly differ from controls. These experiments suggest that the adrenal gland modulates the feeding response to CRF. As replacement with corticosterone (0.75 mg/kg) in total adrenalectomized rats did not restore responsiveness to 5 or 10 micrograms of CRF, we next studied whether the adrenal medulla was responsible for the decreased responsiveness to CRF. In rats lacking the adrenal medulla only, food intake was reduced by a 5 microgram injection of CRF; in sham rats, intake was significantly reduced by doses as low as 0.1 microgram of CRF. An additional experiment examined the effect of gastric vagotomy on the CRF feeding response. Vagotomized rats were as responsive to 5 and 10 microgram injections of CRF as sham rats, which suggests that the effect is not dependent on the vagus nerve. These findings indicate that the adrenal gland, primarily the medulla, plays an intermediate role in the reduction of food intake caused by central injections of CRF. This conclusion is consistent with the known effect of CRF on adrenomedullary discharge.