Cholecystokinin (CCK) may have a transmitter/modulator role in the hypothalamic magnocellular neurosecretory system. In the rat, the supraoptic and paraventricular nuclei display high affinity binding for radiolabelled CCK. Exogenously applied CCK depolarizes supraoptic neurons, acting at postsynaptic CCK-B type receptors. The present study evaluated the ability for the sulfated octapeptide of CCK (CCK-8S), which is a predominate form of this peptide in brain, to evoke release of vasopressin from the neurohypophysis of intra-arterially perfused hypothalamic explants. 3 min applications of 1 microM CCK-8S through the intra-arterial perfusion medium prompted an elevation of vasopressin in samples taken from the neurointermediate lobe in 10 of 14 preparations. Vasopressin levels rose from undetectable baseline values to a peak of 29.5 +/- 6.7 pg/ml (mean +/- S.E.M). This response was dose-dependent and was abolished by pituitary stalk transection (5/5 explants). Locally applied CCK-8S (25-200 pmol) through bilateral infusions onto the ventral surface of the supraoptic nucleus also induced a dose-dependent release of vasopressin (5/7 explants). These observations suggest that CCK can act at receptors located on (or near) the somata of supraoptic nucleus neurons to induce neuronal discharges that are conducted to the neural lobe where they evoke release of vasopressin from neurohypophysial axon terminals.