Recent studies have demonstrated the presence of autoantibodies against α₁-adrenoceptor (α₁-AAB) in the serum of patients with primary hypertension, and that these autoantibodies exert adrenergic-agonist-like effects. However, their role in the development of hypertension remains unclear. The current study determined whether α₁-AAB can cause vascular contraction, and further investigated the cellular receptors that mediate their vasoactivity. Enzyme-linked immunosorbent assay (ELISA) was used to detect α₁-AAB in blood samples collected from 73 patients with primary hypertension and 86 normotensive patients. IgGs were purified from mixed sera from 25 α₁-AAB-positive hypertensive patients and 20 α₁-AAB-negative normotensives, respectively. The vasoconstrictive effect of purified IgG from the sera of either hypertensive or normotensive patients was observed in isolated rat thoracic aorta, coronary artery, renal artery, middle cerebral artery, and mesenteric artery. The effects of α₁-AAB administration on mean arterial blood pressure in vivo were also assessed. The frequency of α₁-AAB presence was considerably higher in patients with primary hypertension than normotensive subjects (34.2 vs. 10.5%, P < 0.01). In isolated thoracic aortic rings, renal artery, middle cerebral artery, and coronary artery segments, α₁-AAB induced vasoconstriction in a concentration-dependent fashion, which can be completely blocked by prazosin, a selective α₁-adrenoceptor antagonist. The mean arterial pressure significantly increased after the administration of α₁-AAB in vivo. Our results demonstrated that the α₁-AAB (which exhibited remarkable effects of vascular contraction in vitro, elevated blood pressure in vivo, and showed no desensitization phenomena) may play a role in both elevating vascular resistance and the development and maintenance of hypertension.