To determine whether the anorexic and the hyperglycemia actions of somatostatin were mediated through the hypothalamic nuclei, rats were infused with somatostatin and normal saline through previously implanted hypothalamic cannulae. Administration of somatostatin (0.5–1.5 µg in 1.0 µl) into the lateral hypothalamus, but not the ventromedial or the anterior hypothalamus, caused a reduction in food consumption without affecting relative water intake (or water-to-food ratio) in conscious rats in a freely moving state. On the other hand, administration of somatostatin into the lateral hypothalamus, but not the anterior or the ventromedial hypothalamus, caused an increase in blood glucose level in rats. This hyperglycemia was antagonized by vagotomy, but not by spinal transection or adrenalectomy. The data indicate that the lateral hypothalamus is the most sensitive site of the somatostatin-induced anorexia and the action of somatostatin on the lateral hypothalamus-vagus efferent activity is also a possible mechanism mediating hyperglycemia in r