The effect of cerebral intraventricular insulin on pancreatic insulin secretion was investigated. An extracorporeal pancreatic blood circuit was established after laparotomy to monitor blood flow and insulin concentration directly from the superior pancreaticoduodenal vein. Phentolamine was infused throughout (0.2 mg./min. intravenously) to block alpha-adrenergic effects of any catecholamine secretion induced by surgical stress. Glucose (1.5 mg./kg./min. intravenously) was infused to maintain a constant baseline stimulation of insulin secretion. Six dogs received insulin and six control dogs received saline through a spinal needle stereotaxically placed into the left lateral cerebral ventricle. After central injection of insulin (0.2 U./kg.) there was a significant increase of pancreatic output as early as five minutes. It is concluded that the pancreatic beta-cells are under the influence of insulin-sensitive cells of the CNS.