We have previously shown that activation of P2x purinoceptors in the subpostremal NTS produces a rapid bradycardia and hypotension. This bradycardia could occur via sympathetic withdrawal, parasympathetic activation, or a combination of both mechanisms. Thus, we investigated the relative roles of parasympathetic activation and sympathetic withdrawal in mediating this bradycardia in chloralose/urethane anesthetized male Sprague Dawley rats. Microinjections of the selective P2x purinoceptor agonist, ,-methylene ATP (25 pmol/50 nL and 100 pmol/ 50 nL), were made into the subpostremal NTS in control animals, after atenolol (2 mg/kg i.v.), a 1 selective antagonist, and after atropine methyl bromide (2 mg/kg i.v.), a muscarinic receptor antagonist. The bradycardia observed with activation of P2X receptors at the low dose of the agonist is mediated almost entirely by sympathetic withdrawal. After ₁ -adrenergic blockade, the bradycardia was reduced to just -5.1±0.5 beats/min versus -28.8±5.1 beats/min in intact animals. Muscarinic blockade did not produce any significant change in the bradycardic response at the low dose. At the high dose both ₁ -adrenergic blockade and muscarinic blockade attenuated the bradycardia similarly, -37.4±6.4 beats/min and -40.6±3.7 beats/min respectively compared to -88.0±11.0 beats/min in control animals. Double blockade of both ₁ -adrenergic and muscarinic receptors virtually abolished the response (-2.5±0.8 beats/min).We conclude that the relative contributions of parasympathetic activation and sympathetic withdrawal are dependent on the extent of P2x receptor activation.