It has generally been assumed that nicotine acts in autonomic ganglia to raise blood pressure. We considered that the pressor effect of nicotine might also involve central mechanisms. We tested this hypothesis in male Sprague-Dawley rats, Wistar-Kyoto (WKY) rats, and spontaneously hypertensive rats (SHR). The animals were anesthetized with urethane and blood pressure was monitored intraarterially. Nicotine was microinjected into various sites in the medulla using stereotaxic technique. While nicotine elicited bradycardia and hypotension in the nucleus tractus solitarii and area postrema, its injection into the rostral ventrolateral medulla (RVLM) produced a does-related and long-lasting increase in both systolic and diastolic pressure. This pressor effect of nicotine was not influenced by muscarinic receptor blockade (atropine 2.9 mumol intravenously), but was completely abolished by local nicotinic receptor blockade (hexamethonium 2.7 nmol). The WKY rats responded to nicotine administration into the RVLM with approximately equivalent changes in systolic and diastolic blood pressure and heart rate. The SHR was more sensitive to nicotine than WKY rats in producing pressor effect when it was injected into the RVLM. Thus, the increase of blood pressure consequent to nicotine is acting through nicotinic receptors in RVLM. These findings suggest a role for medullary nicotinic receptors in neural cardiovascular control and reveal an enhanced sensitivity to this effect of nicotine in the spontaneously hypertensive rat.