We have examined the hypothesis that MSH secretion in the rat is under a tonic inhibitory control by the central nervous system. Electrothermic lesions were made in the medio-basal hypothalamus (m.b.h.) which destroyed the hypothalamo-hypophyseal connexions. Plasma and pituitary alpha-MSH wwere measured using a sensitive and specific radioimmunoassay technique. Pituitary alpha-MSH content decreased to 17% of control levels 24 hr after the lesion and returned to normal by 7 days. Plasma alpha-MSH was maximally elevated 15 min after the lesion, and returned to normal by 2 hr. No further change over control levels was found for the remainder of the experiment (98 days). The similarity of the plasma alpha-MSH response after m.b.h. lesions to that found previously after administration of long acting dopamine receptor blocking drugs suggests that these lesions may interrupt impulse flow in dopaminergic tubero hypophyseal neurones which are thought to be important in the inhibitory control of MSH secretion in the rat. From our present results it seems that the rat pituitary, unlike that of lower vertebrates, is able to re-establish basal MSH secretion very quickly after disconnexion from central control.