Vanilloid type 1 (VR-1) receptors are stimulated by capsaicin and hydrogen ions, the latter being a metabolic by-product of muscular contraction. Capsaicin, injected into the arterial supply of skeletal muscle reflexly increases mean arterial pressure and heart rate. We tested the hypothesis that activation of VR-1 receptors during static contraction contributed to the elicitation of the exercise pressor reflex. We established a dose of Iodoresinaferatoxin (IRTX), a VR-1 receptor antagonist, which blocked the pressor response to capsaicin injected into the arterial supply of skeletal muscle. Specifically, in 8 decerebrated cats we compared the pressor responses to capsaicin (10 µg) injected into the right popliteal artery, which was subsequently injected with IRTX (100µg), with those to capsaicin injected into the left popliteal artery, which was not injected with IRTX. The pressor response to capsaicin injected into the right popliteal artery averaged 49 ± 9 mmHg before IRTX and 9 ± 2 mmHg after (P <0.05). In contrast, the pressor response to capsaicin injected into the left popliteal artery averaged 46 ± 10 mmHg "before" and 43 ± 6 mmHg "after" (P >0.05). We next determined if VR-1 receptors mediated the pressor response to static contraction of the triceps surae muscles. Data from 8 decerebrated cats showed that during contraction without circulatory occlusion the pressor response before IRTX (100 µg) averaged 26 ± 3 mmHg, whereas it averaged 22 ± 3 mmHg (P>0.05) after IRTX. We also determined if IRTX attenuated the pressor responses to contraction with circulatory occlusion. Data from 7 decerebrated cats showed that during contraction with circulatory occlusion the pressor responses averaged 35 ± 3 mmHg before IRTX injection and 49 ± 7 mmHg after IRTX injection. We conclude that VR-1 receptors play little if any role in evoking the exercise pressor reflex, regardless of whether the contracting muscles are freely perfused or their circulation is occluded.