A series of six experiments examined the neural loci responsible for caerulein's suppression of eating. Caerulein is a decapeptide chemically and physiologically similar to cholecystokinin, a naturally occurring gut hormone in rats. Rats with lesions in the ventromedial hypothalamus (VMH) showed reduced sensitivity to caerulein (1 mug/kg); rats with lateral hypothalamic (LH) destruction showed heightened sensitivity. Microinjections of caerulein into the VMH, but not into the LH, limited feeding. Finally, tritiated caerulein was selectively bound to tissue in the VMH. The results are discussed in terms of the hypothesis that the VMH manages postprandial inhibition in the rat.