Objective: The mechanisms underlying the pressor response to nicotine are incompletely understood. Although sympatho-adrenergic activation plays a major role, the relative contribution of adrenal vs. neurally released catecholamines and the possible role of non-adrenergic factors (e.g. vasopressin release) is not established. Methods: We examined the cardiovascular responses to graded i.v. injections of nicotine (1 to 100 μg kg⁻¹) in conscious Wistar–Kyoto rats under control conditions and (i) after chemical sympathectomy by 6-hydroxydopamine, which destroys sympathetic endings but spares the adrenal medulla; (ii) after an α-adrenergic blockade by phenoxybenzamine; (iii) after a V₁ vasopressin receptor blockade by a specific antagonist. Results: In control rats, nicotine caused a dose-dependent tachycardiac and pressor response. Both responses were abolished by sympathectomy, whereas the α-blockade left the tachycardiac response unaffected but inhibited the pressor response; the V₁ vasopressin receptor blockade had no effect on either the tachycardiac or pressor response. Conclusions: We conclude that in the conscious rat: (1) the pressor response to nicotine mainly depends on peripheral α-adrenergically-mediated vasoconstriction; (2) the vasomotor effect is caused by neural rather than adrenomedullary catecholamine release; (3) the nicotine-induced increase in heart rate (and presumably cardiac output) is per se unable to raise blood pressure, and (4) the nicotine-induced release of vasopressin plays no significant role in the pressor response.