Several experiments are reported in which insulin or glucose was administered intravenously to anesthetized dogs. Plasma and cerebrospinal fluid levels of glucose and immunoreactive insulin were determined at several intervals before and after the administrations. Intravenous insulin (0.2 U/kg) administered as either a pulse or a 1-h infusion caused a large increase of plasma insulin, but a relatively small increase of cerebrospinal fluid insulin. When endogenous insulin was elevated by the administration of glucose (100 mg/kg), cerebrospinal fluid insulin changed only slightly. A significant correlation was found between steady-state plasma and CSF endogenous insulin levels. The results are interpreted to indicate that the level of insulin in the cerebrospinal fluid reflects basal plasma level plus an integral over time of the insulin response to challenge. The implications of such a system are discussed.