Exp Physiol 99.2 (2014) pp 403–413 403 Research Paper Research Paper Exercise training effects on hypoxic and hypercapnic ventilatory responses in mice selected for increased voluntary wheel running Scott A. Kelly 1,2 , Enrico L. Rezende 1 , Mark A. Chappell 1 , Fernando R. Gomes 1 , Erik M. Kolb 1 , Jessica L. Malisch 1 , Justin S. Rhodes 3 , Gordon S. Mitchell 4 and Theodore Garland Jr 1 1 Department of Biology, University of California, Riverside, Riverside, CA 92521, USA 2 Department of Zoology, Ohio Wesleyan University, Delaware, OH 43015, USA 3 Deptartment of Psychology, Beckman Institute, University of Illinois, Urbana, IL 61801, USA 4 Department of Comparative Biosciences, University of Wisconsin, School of Veterinary Medicine, Madison, WI 53706, USA New Findings  What is the central question of this study? We used experimental evolution to determine how selective breeding for high voluntary wheel running and exercise training (7–11 weeks) affect ventilatory chemoreflexes of laboratory mice at rest.  What is the main finding and its importance? Selective breeding, although significantly affecting some traits, did not systematically alter ventilation across gas concentrations. As with most human studies, our findings support the idea that endurance training attenuates resting ventilation. However, little evidence was found for a correlation between ventilatory chemoreflexes and the amount of individual voluntary wheel running. We conclude that exercise ‘training’ alters respiratory behaviours, but these changes may not be necessary to achieve high levels of wheel running. Ventilatory control is affected by genetics, the environment and gene–environment and gene– gene interactions. Here, we used an experimental evolution approach to test whether 37 generations of selective breeding for high voluntary wheel running (genetic effects) and/or long-term (7–11 weeks) wheel access (training effects) alter acute respiratory behaviour of mice resting in normoxic, hypoxic and hypercapnic conditions. As the four replicate high-runner (HR) lines run much more than the four non-selected control (C) lines, we also examined whether the amount of exercise among individual mice was a quantitative predictor of ventilatory chemoreflexes at rest. Selective breeding and/or wheel access significantly affected several traits. In normoxia, HR mice tended to have lower mass-adjusted rates of oxygen consumption and carbon dioxide production. Chronic wheel access increased oxygen consumption and carbon dioxide production in both HR and C mice during hypercapnia. Breathing frequency and minute ventilation were significantly reduced by chronic wheel access in both HR and C mice during hypoxia. Selection history, while significantly affecting some traits, did not systematically alter ventilation across all gas concentrations. As with most human studies, our findings support the idea that endurance training (access to wheel running) attenuates resting ventilation. However, little evidence was found for a correlation at the level of the individual variation between ventilatory chemoreflexes and performance (amount of individual voluntary wheel running). C  2013 The Authors. Experimental Physiology C  2013 The Physiological Society DOI: 10.1113/expphysiol.2013.076018