Responses to the P2x selective agonist, α,β-Methyl-ATP were investigated in the pulmonary, mesenteric, and hindlimb vascular beds of the cat. Under conditions of constant blood flow, α,β-Methyl-ATP induced dose-dependant increases in perfusion pressure in all vascular beds studied. In the pulmonary vascular bed of the cat α,β-Methyl-ATP was approximately 3-fold more potent than the thromboxane A2 mimic, U-46619. In the mesenteric vascular bed, vasoconstrictor responses to α,β-Methyl-ATP were 10-100 fold less potent than responses to U-46619. When injected into the hindlimb perfusion circuit, α,β-Methyl-ATP produced only modest vasoconstrictor responses which were 100-1000 fold less potent than U-46619. Vasoconstrictor responses to α,β-Methyl-ATP were attenuated by adminstration of PPADS, a P2x selective antagonist but not by the angiotensin II AT1 receptor antagonist, candesartan, the alpha-adrenergic blocking agent, phentolamine, the cyclooxygenase inhibitor, meclofenamate, or the endothelin ETA/ETB receptor antagonist, bosentan. These data suggest that α,β-Methyl-ATP has potent vasoconstrictor activity in the pulmonary and mesenteric vascular beds of the cat, and modest vasoconstrictor activity in the hindlimb vascular bed. These data further suggest the response to α,β-Methyl-ATP are mediated by P2x receptors. These data further suggest that P2x receptor distribution in the cat depends on the vascular bed.