The role of the paraventricular (PVN) and ventromedial (VMN) hypothalamic nuclei in the activation and inhibition of the pituitary-adrenocortical system was studied in chronic experiments on rabbits. The functioning of the pituitary-adrenocortical system was estimated by changes in blood corticosteroid levels. PVN and VMN lesions resulted in a reduction of the stress-induced corticosteroid rise. VMN lesions resulted in smaller changes of the stress-induced response than PVN lesions while combined VMN and PVN lesions did not cause a larger reduction of the stress-induced activation than lesions of either area. The data obtained confirm that the PVN and VMN are connected in series. Hydrocortisone (100 μg/kg) administered intravenoously 5 min before immobilization inhibits the stress-induced corticosteroid rise in intacts rabbits. PVN and VMN lesions result in a reduction of the hydrocortisone inhibitory effect, PVN lesions having a greater effect than VMN ones. The PVN is of greater importance in both the activation and the inhibition of the pituitary-adrenocortical system than the VMN.