Somatostatin-28 (SS-28) acted within the central nervous system (CNS) to produce a dose-dependent elevation of mean arterial pressure (MAP), a reduction of heart rate (HR), and an elevation of the plasma concentration of vasopressin. SS-28 given intravenously did not affect MAP or HR. Furthermore, these changes of cardiovascular functions were not prevented by systemic passive immunization against SS-28, thus supporting a CNS site of action. Microinjections of SS-28, in amounts ineffective when given into the lateral cerebroventricle or other brain parenchymal areas, into the paraventricular nucleus of the hypothalamus produced significant elevations of MAP. Neither ganglionic blockade with chlorisondamine nor treatment with the α-adrenergic receptor antagonist, phentolamine, prevented SS-28-induced changes of cardiovascular function; however, treatment of animals with the vasopressin antagonist [1-deaminopenicillamine, 2-(0-methyl)Tyr]-vasopressin completely prevented SS-28-induced elevation of MAP and slowing of HR. These results suggest that SS-28 acts within the CNS to increase MAP and decrease HR by stimulating pituitary vasopressin secretion