It has recently been reported that prostaglandin (PG)F_2α produces diruesis and natriuresis when given directly into a lateral ventricle of the brain in rabbits (Kook et al). In this study attempts were made to elucidate the mechanism of the natriuresis utilizing dogs. In mongrel dogs of both sexes weighing 9-l2kg, a lateral ventricle of the cerebrum was cannulated and the agent was delivered in less than 0.2ml of 0.9% saline. PGE_2α, 100μg, ivt, elicited mild diuresis, while glomerular filtration rate and systemic blood pressure remained unchanged. In 8 chloralso-anesthetized, hydrated dogs undergoing water diuresis, ivt PGE_2α produced antidiuresis concomitant with marked natriuresis, which resembles the action of large doses of Arginine vasopressin in doses of 0.3-1.5mu/kg/min produced marked natriuresis. In 9 experiments, PGE_2α was given intraventricularly during the maximal diuresis induced by ADH. The kidney responded with significant natriuresis though less marked and transient than during water diuresis. It is thus concluded that beside ADH still other natriuretic factor(s) may be involved in the natriuresis induced by ivt PGE_2α in the dog.