Wood HE, Levine BD, Babb TG. Ventilatory responses to exercise and hypercapnia following 18 days of head-down rest. Aviat Space Environ Med 2009; 80:395–9. Introduction: The effects of head-down rest (HDR) and microgravity on cardiovascular control have been widely studied; however, their effects on ventilatory control are less clear. An increased ventilatory response to exercise and/or to hypercapnia (HCVR) could cause significantly increased ventilatory demand and/or dyspnea, and thus limit the ability of flight crew to perform high-intensity exercise during or after spaceflight. Based on limited previous studies, we hypothesized that the ventilatory response to exercise would be increased, while the HCVR would be decreased after HDR. Methods: In 21 healthy subjects, ventilatory responses to submaximal exercise and to hypercapnia were tested before and immediately after 18 d of HDR. Subjects were randomly assigned to either daily supine cycle exercise (Exercise group; N = 14, 2 women) or no exercise (Rest group; N = 7, 1 woman) during HDR. Results: The exercise ventilatory response (<inline-graphic xlink:href="395inf1.gif"/>e/<inline-graphic xlink:href="395inf1.gif"/>co₂) and the HCVR were unchanged following HDR in both groups. However, ventilation was significantly elevated after HDR at rest, during submaximal exercise, and while breathing 6% CO₂. End-tidal Pco₂ was significantly reduced at rest, during submaximal exercise, and while breathing 3% CO₂, indicating a decrease in the CO₂ set point. Discussion: Although HDR had no effect on the ventilatory responses to exercise and hypercapnia, the CO₂ set point appeared to be reduced, suggesting an increase in drive to breathe that occurred regardless of whether or not subjects undertook exercise during HDR. These preliminary results indicate that further study of the effects of HDR on ventilatory control is warranted.