Static muscle contraction increases ATP release into the muscle interstitial space. Elevated ATP in muscle stimulates thin fiber muscle afferents and increases blood pressure via engagement of purinergic P2X receptors. In addition, ATP activates P2X receptors and enhances cardiovascular responses induced by stimulation of muscle mechanoreceptors. In this report, we examined if elevated muscle temperature would attenuate and reduced temperature would potentiate P2X effects on reflex muscle responses. ,-methylene ATP (, me ATP) was injected into the arterial blood supply of hindlimb muscle to stimulate P2X receptors and muscle stretch was induced to activate mechanically sensitive muscle afferents as , me ATP was injected in 10 anesthetized cats. Femoral arterial injection of , me ATP (1.0 mM) increased mean arterial pressure (MAP) by 35±5 (35°C), 26±3 (37°C) and 19±3 mmHg (39°C; P<0.05 vs 35°C), respectively. Muscle stretch (2 kg) elevated MAP. The MAP response was significantly enhanced 34% and 36% when , me ATP (0.2 mM) was arterially infused 5 min before muscle stretch at 35 and 37°C, respectively. However, as muscle temperature was reached to 39°C the stretch-evoked response was augmented only 6% by , me ATP injection and the response was significantly attenuated as compared with the response with muscle temperature of 35 and 37°C. In addition, we also examined effects of muscle temperature on , me ATP enhancement of the cardiovascular responses to static muscle contraction while the muscles were freely perfused and the circulation to the muscles was occluded. As muscle temperature was 37°C, arterial injections of , me ATP significantly augmented contraction evoked MAP response by 49% (freely perfused) and 53% (ischemic condition), respectively. It is noted that this effect was significantly attenuated at muscle temperature of 39°C. These data indicate that the effect of P2X receptor on reflex muscle response is sensitive to alternations of muscle temperature and that elevated temperature attenuates the response.