Bilateral occlusion of the common carotid arteries of urethane-anesthetized rats evoked a pressor response of 14 +/- 1 mm Hg. Injection into the lateral cerebral ventricle of neostigmine (0.2-1.0 microgram) or physostigmine (10-15 microgram) caused a dose-dependent increase in basal blood pressure and in the magnitude of the carotid artery occlusion (CAO) pressor reflex. Neostigmine (1 microgram) and physostigmine (15 microgram) caused nearly maximal and approximately equal degrees of cholinesterase inhibition in several brain regions. The recovery of the cardiovascular parameters and of brain cholinesterase activity was significantly faster following physostigmine compared to neostigmine. Prior intracerebroventricular injection of atropine (0.3 microgram) or hemicholinium-3 (20 microgram) prevented the increases in basal pressure and the CAO pressor response. Potentiation of the CAO reflex also followed injection of physostigmine or neostigmine into the posterior hypothalamic nucleus and of injection of physostigmine intravenously. Injection of atropine bilaterally into ther posterior hypothalamic nucleus prior to intravenous injection of physostigmine prevented the potentiation of the CAO reflex but not the increase in basal blood pressure. These results indicate that acetylcholine in the posterior hypothalamic nucleus serves as a neurotransmitter in a pathway which can potentiate the pressor response to carotid artery occlusion and thus modulate baroreceptor reflexes.