Abstract--The -1 adrenergic receptors (₁ARs) are critical in sympathetically mediated vasoconstriction. The specific role of each ₁AR subtype in regulating vasoconstriction remains highly controversial. Limited pharmacological studies suggest that differential ₁AR responses may be the result of differential activation of junctional versus extrajunctional receptors. We tested the hypothesis that the _1BAR subtype is critical in mediating sympathetic junctional neurotransmission. We measured in vivo integrated cardiovascular responses to a hypotensive stimulus (induced via transient bilateral carotid occlusion [TBCO]) in _1BAR knockout (KO) mice and their wild-type (WT) littermates. In WT mice, after dissection of the carotid arteries and denervation of aortic baroreceptor buffering nerves, TBCO produced significant pressor and positive inotropic effects. Both responses were markedly attenuated in _1BAR KO mice (change systolic blood pressure 46±8 versus 11±2 mm Hg; percentage change in the end-systolic pressure-volume relationship [ESPVR] 36±7% versus 12±2%; WT versus KO; P<0.003). In vitro ₁AR mesenteric microvascular contractile responses to endogenous norepinephrine (NE; elicited by electrical field stimulation 10 Hz) was markedly depressed in _1BAR KO mice compared with WT (12.4±1.7% versus 21.5±1.2%; P<0.001). In contrast, responses to exogenous NE were similar in _1BAR KO and WT mice (22.4±7.3% versus 33.4±4.3%; NS). Collectively, these results demonstrate a critical role for the _1BAR in baroreceptor-mediated adrenergic signaling at the vascular neuroeffector junction. Moreover, _1BARs modulate inotropic responses to baroreceptor activation. The critical role for _1BAR in neuroeffector regulation of vascular tone and myocardial contractility has profound clinical implications for designing therapies for orthostatic intolerance.