Intracerebroventricular injection of corticotropin-releasing factor (CRF) in animals activates behavioral, motor, metabolic and sympathetic responses similar to those seen with stress. To explore the pharmacokinetics of this peptide in the primate ventricular CSF, we determined the clearance of ovine 125I-CRF from the CSF and compared it to that of 111In-DTPA, a substance cleared by bulk flow. 125I-CRF was cleared from the ventricular fluid sixfold more rapidly than bulk flow. This suggests that the CSF may be a pathway for physiological distribution of this releasing factor to active sites within the central nervous system, and that a mechanism exists for active removal of CRF from the ventricular CSF.