The presence of a natriuretic factor in the plasma of rats in which a 350 mM Na (high Na) artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle was tested. Blood was obtained from control rats and rats which received an infusion of high Na CSF intraventricular (IVT) for 15 min. The plasma was incubated for 30 min at room temperature, acidified, placed in a boiling-water bath, and then centrifuged. The plasma supernate was assayed for natriuretic activity in pentobarbital anesthetized bioassay rats. Sodium excretion increased 6.5 +/- 1.1 mueq/kg X min in rats which received an infusion of a control saline solution, 13.3 +/- 3.2 mueq/kg X min in rats which received infusion of control plasma supernates, and 32.1 +/- 8.3 mueq/kg X min in those rats which received plasma supernates from rats infused with high Na CSF IVT. Blood pressure was unchanged in all groups. The increment in sodium excretion elicited by plasma supernate from the high Na IVT group was significantly greater than that elicited by either control saline solution or control plasma extracts. Therefore, it is concluded that a heat-stable and nonpressor natriuretic factor is present in the plasma of rats infused IVT with high Na CSF.