The intracisternal administration of insulin (0.2 U./kg.) to anesthetized dogs resulted in an increase of arterial immunoreactive insulin and a decrease of plasma glucose relative to a control injection. The arterial responses were significantly attenuated when the insulin was administered to the cisternum of subdiaphragmatically vagotomized dogs. When cerebrospinal fluid glucose was lowered by injecting pneumococcal neuraminidase intracisternally, no peripheral hyperinsulinemia resulted, indicating that increased spinal fluid insulin and its consequent increase of glucose uptake, rather than decreased spinal fluid glucose, is necessary to elicit the vagally mediated insulin secretion and hypoglycemia. It is hypothesized that increased spinal fluid insulin causes an increased glucose uptake of some glucoregulatory area of the brain and that the elicited reflex is vagally mediated pancreatic insulin secretion.