In vivo somatostatin inhibits exocrine pancreatic secretion. In in vitro experiments, such as the isolated perfused pancreas, somatostatin fails to inhibit exocrine pancreatic secretion. This suggests an indirect action of somatostatin, such as modulation of neural regulation. In the anesthetized rat we tested the inhibitory capacity of somatostatin in the presence of neural blockade in vivo. Neither the drugs given intravenously--phentolamine, propranolol, atropine and naloxone--nor vagotomy were able to prevent somatostatin-induced inhibition of exocrine pancreatic secretion. We conclude that somatostatin-induced inhibition of exocrine pancreatic secretion is not dependent on intact extrinsic innervation.