Neural control of the circulatory and ventilatory responses to exercise has been an intriguing area of investigation for well over 100 years. However, development of experimental protocols that clarify mechanisms and their relative importance has proved difficult because of the likelihood of redundancy and the complexity of central integration. In this issue of Experimental Physiology, Lam, Greenhough, Nazari, White, & Bruce (2019) met this challenge with an elegant and cleverly designed study in humans that improves our understanding of the contribution of metabolically sensitive neural feedback from active skeletal muscle to the cardiorespiratory response to dynamic exercise. Ventilation and heart rate responses to exercise occur rapidly to a level well matched to the workload. Descending neural signals from higher brain centres (i.e. central command) have a prominent role in increasing ventilation and heart rate in proportion to the effort exerted (Goodwin, McCloskey, & Mitchell, 1972). When examining the contribution of metabolically sensitive neural feedback from active skeletal muscle (i.e. the metaboreflex) in isolation after exercise, which effectively increases blood pressure, the ventilatory and heart rate responses generally trend towards resting values. Given this, the observation that ventilation and heart rate rapidly return towards resting levels during metaboreflex isolation (i.e. postexercise ischaemia) has led some to suggest that the muscle metaboreflex has little influence on both ventilation and heart rate. Countering evidence shows a contribution of the afferent feedback from contracting skeletal muscle to the ventilatory and heart rate response to dynamic leg exercise that is attenuated by pharmacological blockade (Amann et al. 2010). These findings seem to suggest that the metaboreflex can contribute to the ventilatory response to exercise, but only in certain conditions. The study by Lam et al. (2019) provides insight into this mechanism by demonstrating metaboreflex control of exercise ventilation and heart rate only when central command is engaged, i.e. during exercise. To demonstrate this, the authors used an innovative and creative study protocol, in which cardiorespiratory responses to left-legged cycling were followed by right-legged cycling with and without left leg postexercise circulatory occlusion (PECO). Relative to baseline, ventilation was elevated during leg cycling, as expected, but was heightened further during concomitant PECO, particularly at higher workloads. Indeed, ventilation returned to baseline when PECO was performed in a separate protocol without right-legged cycling. Central respiratory drive is modified by many afferent inputs during exercise. However, chemosensitive structures in the medulla and carotid bodies responsible for ventilatory responses to hypoxia and hypercapnia probably make a small contribution to the ventilatory response to mild- and moderate-intensity exercise because arterial , and pH remain relatively constant. Indeed, end-tidal CO2 () was not increased with higher intensity single-legged cycling. In fact, single-legged cycling combined with PECO significantly reduced , probably as a result of greater ventilation relative to CO2 production. Thus, if lower arterial were to be confirmed ( is not necessarily equivalent to arterial ), it would suggest opposite signalling from the muscle metaboreflex and central chemoreflex and perhaps an overall underestimation of metaboreflex-mediated increases in ventilation. However, little is known regarding the potential interaction between the muscle metaboreflex and central and peripheral chemoreceptor input to modulate exercise ventilation. Advancements in the field often create more questions than answers, and the study by Lam et al. (2019) is no exception. An exaggerated ventilatory response to exercise is characteristic of patients with heart failure, chronic obstructive pulmonary disease and pulmonary hypertension. The obvious question is, to what extent does the metaboreflex contribute? Also, exaggerated sympathetic responses (not assessed in the study by Lam et al., 2019) to isolated muscle metaboreflex activation have been documented in patient populations with high prevalence, such as hypertension, heart failure and diabetes. Future studies are needed to determine the extent to which the interaction between the metaboreflex and central command augments the sympathetic response beyond what is observed during isolated metaboreflex activation in these patient populations. To this end, the authors are to be commended on moving a step forwards in our understanding of the role of the skeletal muscle metaboreflex in controlling ventilation and heart rate during exercise in healthy humans.