Vanilloid spice principles, including capsaicin, stimulate vasoconstriction in the rat hindlimb perfused at constant flow and, depending on dose, either stimulate or inhibit oxygen consumption by this vascular bed. We now present metabolic and functional evidence for two different vanilloid (VN1 and VN2) receptor types. These receptors can be distinguished on the basis of their differing agonist affinity for capsaicin, their different calcium and oxygen dependencies for inducing vasoconstriction, and whether they stimulate, or inhibit, oxygen consumption. The higher affinity vanilloid receptor, VN1 can be distinguished on the basis of initiating vasoconstriction at low doses of capsaicin and simultaneously stimulating oxygen consumption. Its apparent biological function is dependent on the presence of oxygen and external calcium. In contrast, the lower affinity receptor, VN2 induces vasoconstriction associated with inhibition of oxygen consumption. Its vasoconstriction action can occur independently of either external calcium ions, or the presence of oxygen in the perfusate.