The effects of insulin administration via intracerebroventricular (ICV), third ventricular (TV) and intracisternal (IC) routes on the urine output and sodium excretion have been studied in mongrel dogs. The central administration of insulin resulted in a significant increase in urine output and sodium excretion. This diuresis and natriuresis was not observed in animals which had undergone either spinal-cord transectomy or adrenalectomy. The insulin-sensitive receptors for this diuresis and natriuresis seem to be present in the vicinity of the fourth-ventricle of the brain. The observations in the present study suggest that the probable efferents might be the sympathetic fibers in the spinal-cord. The centrally administered insulin inhibits the secretion of some substance from the adrenal cortex, which in turn results in the diuresis and natriuresis in animals.