In anesthetized or decerebrated animals, the exercise pressor reflex is evoked by static contraction of the hind limb muscles and results in increased arterial pressure, heart rate, myocardial contractility and ventilation. The sensory arm of the reflex is comprised of group III and IV muscle afferents (McCloskey & Mitchell, 1972). The former are thinly myelinated and are thought to be primarily mechanically sensitive whereas the latter are unmyelinated and thought to be primarily metabolically sensitive (Kaufman et al., 1983). Although several metabolic by-products of contraction are thought to be involved in stimulating group IV metaboreceptors, the receptors responsible are still being investigated. Likewise, metabolic by-products of contraction have also been shown to sensitize group III afferents, and the receptors responsible for it are still under investigation. In the experiments to be described, we have focused on the acid sensitive ion channel (ASIC), which is stimulated by lactic acid, and the purinergic (P) 2 channel, which is stimulated by ATP. Both lactic acid and ATP are well established metabolic by-products of contraction, and their concentrations have been shown to increase in the interstium of muscle during both static contraction under freely perfused conditions and during static contraction under ischemic conditions. We have found that blockade of the P2 channel with PPADS attenuated both metabolic and the mechanical components of the exercise pressor reflex (Kindig et al., 2006;Kindig et al., 2007). Similarly, we found that blockade of the ASIC channel with either amiloride or a variety of antagonists specific to the ASIC 3 channel attenuated the metabolic component of the reflex (Hayes et al., 2008). In addition, we have recorded the impulse activity of group III and IV afferents with endings in the triceps surae muscles while decerebrated cats were made to walk on a treadmill. A precollicular-postmamillary decerebration was performed while the lungs were ventilated with isofluorane (5%) in oxygen. Walking was induced by electrical stimulation of the mesencephalic locomotor region, a maneuver which recruited alpha motoneurons from slow to fast as well as caused them to fire asynchronously. Both effects are known to be displayed by alpha motoneurons during dynamic exercise in intact conscious cats. We found that most group III afferents responded in synchrony with the contraction phase of the step cycle, whereas most group IV afferents responded irregularly with respect to the step cycle (Hayes et al., 2006). Moreover, the responses to dynamic exercise by the group III afferents were prevented by gadolinium, which blocks mechanogated channels, whereas the responses to exercise by the group IV afferents were not blocked by gadolinium (Hayes et al., 2009). During treadmill walking, the triceps surae muscles increased their oxygen consumption only two and half fold, a level which does not appear to be consistent with a mismatch between metabolic demand and blood/oxygen supply. This latter finding suggests that group IV afferents, although capable of responding to ischemic stimuli, may also be capable of responding to a muscle metabolite that is not generated by a mismatch between blood/oxygen demand and supply in exercising muscles.