Corticotropin-releasing factor (CRF) has been administered into the third ventricle of sham-operated and ventromedial hypothalamic (VMH)-lesioned rats in acute and chronic experiments. After a single 5-microgram injection of CRF, there was an acute reduction of food intake in both sham-operated and VMH-lesioned rats that persisted for 3 h. The effect was still present in the VMH-lesioned rats between 3 and 6 h but had dissipated in the sham-operated controls. Guanosine 5'-diphosphate (GDP) binding to mitochondria from interscapular brown adipose tissue was used as an index of thermogenic activity in this tissue. In 21-h food-deprived rats, GDP binding was significantly lower in VMH-lesioned than in sham-operated animals. Although the mean increase in sham-operated animals was increased, this was not significantly different from saline-injected controls. In the VMH-lesioned rats, however, CRF acutely increased GDP binding to values not different than those of the sham-operated controls. Serum corticosterone was significantly lower in the VMH-lesioned rats, but both groups showed a significant stimulation by CRF during a 7-day infusion of CRF (4.8 micrograms/day) into the third ventricle. Food intake was significantly depressed in the VMH-lesioned animals that received CRF, from values of 35 g/day to approximately 25 g/day. Body weight showed a slow steady decrease, having fallen by nearly 15 g at the end of the 7-day infusion period. In contrast the mean value in the VMH-lesioned controls had significantly higher in CRF-infused animals.(ABSTRACT TRUNCATED AT 250 WORDS)