Our previous studies concluded that stimulation of NTS A_2a receptors evokes preferential hindlimb vasodilation mainly via inducing increases in preganglionic sympathetic nerve activity (pre-ASNA) directed to the adrenal medulla. This increase in pre-ASNA causes the release of epinephrine and subsequent activation of -adrenergic receptors which are preferentially located in the skeletal muscle vasculature. Selective activation of NTS A₁ adenosine receptors evokes variable, mostly pressor effects and increases both pre-ASNA as well as lumbar sympathetic activity which is directed to the hindlimb. These counteracting factors may have opposite effects on the hindlimb vasculature resulting in mixed vascular responses. Therefore in chloralose/urethane anesthetized rats we evaluated the contribution of vasodilator vs. vasoconstrictor effects of stimulation of NTS A₁ receptors on the hindlimb vasculature. We compared the changes in iliac vascular conductance evoked by microinjctions into the NTS of the selective A₁ receptor agonist, N⁶-Cyclopentyladenosine (CPA, 330 pmol in 50 nl volume) in intact animals with the responses evoked following -adrenergic blockade, bilateral aderenalectomy, bilateral lumbar sympathectomy and combined adrenalectomy + lumbar sympathectomy. In intact animals stimulation of NTS A₁ receptors evoked variable effects: increases and decreases in MAP and iliac conductance with prevailing pressor and vasoconstrictor effects. Peripheral -adrenergic receptor blockade and bilateral adrenalectomy eliminated the depressor component of the responses, markedly potentiated iliac vasoconstriction and tended to increase the pressor responses. Lumbar sympathectomy tended to decrease the pressor and vasoconstrictor responses. Following bilateral adrenalectomy plus lumbar sympathectomy a marked vasoconstriction in iliac vascular bed still persisted suggesting that the vasoconstrictor component of the response to stimulation of NTS A₁ receptors is mediated mostly via circulating factors (e.g. vasopressin, angiotensin II, or circulating catecholamines released from other sympathetic terminals). These data strongly suggest that stimulation of NTS A₁ receptors exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and -adrenergic vasodilation versus vasoconstriction mediated by neural and humoral factors.