In the present study, we examined the effect of intracerebroventricularly injected choline on plasma ACTH (adrenocorticotrophin) and beta-endorphin levels in conscious rats. The intracerebroventricularly injection of choline (50-150 mu g) elevated plasma ACTH levels in a dose-dependent manner. Plasma beta-endorphin levels were also significantly increased. Pretreatment of rats with mecamylamine (50 mu g; intracerebroventricularly), the nicotinic receptor antagonist, completely inhibited the ACTH and beta-endorphin response to choline (150 mu g; intracerebroventricularly). An antagonist of the muscarinic receptor, atropine (10 mu g; intracerebroventricularly), failed to alter these effects. Pretreatment of rats with hemicholinium-3 (20 mu g; intracerebroventricularly), a drug which inhibits the uptake of choline into cholinergic neurons, abolished the choline-induced increases in both plasma ACTH and beta-endorphin levels. These results indicate that choline can increase plasma concentrations of ACTH and beta-endorphin through the activation of central nicotinic acetylcholine receptors.