125I-Labeled cholecystokinin octapeptide ([125I]CCK-OP) diffuses rapidly by a non-carrier-mediated mechanism into the peripheral blood following injection into the lateral ventricle of a rabbit. In contrast, no [125I]CCK-OP was observed in the CSF following intravenous injection. This unidirectional free transport mechanism from CSF to blood may apply to other neuropeptides as well.