In the present study, both the effects of intracerebroventricular (i.c.v.) injection of cytidine-5'-diphosphate choline (CDP-choline) on plasma vasopressin levels and the choline involvement of these effects were investigated. I.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 mumol) increased plasma vasopressin levels dose- and time-dependently. I.c.v. injection of equimolar dose of choline (1 mumol) produced similar vasopressin response. However equimolar dose of cytidine (1 mumol; i.c.v.), the other hydrolysis product of CDP-choline, did not affect plasma vasopressin levels. Pretreatment of rats with hemicholinium-3, neuronal high affinity choline uptake inhibitor (20 mug; i.c.v.) blocked the vasopressin response to i.c.v. CDP-choline (1 mumol). Pretreatment of rats with mecamylamine (50 mug; i.c.v.), a nonselective nicotinic receptor antagonist, abolished the increase in plasma vasopressin induced by CDP-choline while atropine (10 mug; i.c.v.), nonselective muscarinic receptor antagonist, failed to change the response. In conclusion, intracerebroventricularly injected CDP-choline can increase plasma vasopressin levels by activating central nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms.