Abstract General characteristics of the cardiovascular response to intracerebroventricular (i.c.v.) injection of acetylcholine (ACh) and the mechanisms mediating this response were studied. Acetylcholine produced a pressor response which was sometimes followed by a prolonged depressor response. The vascular response to ACh. in the majority of experiments, was not accompanied by marked changes in heart rate. The pressor effect of ACh was abolished after transsection of the spinal cord, intracerebroventricular administration of atropine or nicotine and intravenous administration of phenoxybenzamine, tolazoline or methylatropine. Furthermore, the pressor response to ACh was reduced after bilateral adrenalectomy or intravenous injection of bretylium. However, bilateral cutting of the vagosympathetic trunks and intracerebroventricular or intravenous administration of hexamethonium did not affect the pressor response to ACh. It is concluded that the pressor effect of ACh results from the activation of the central muscarinic receptor sites, which evokes the activation of the muscarinic receptors in the sympathetic ganglia and the adrenal medulla followed by the release of catecholamines from adrenergic nerve terminals and the adrenal medulla. In the rat sympathetic ganglia and the adrenal medulla, in addition to the nicotinic receptors, the muscarinic receptors can play the role of the main pathway in ganglionic transmission.