Ventilatory control undergoes profound changes on ascent to high attitude. We hypothesized that the fall, in citric acid cough threshold seen on ascent to attitude is mediated by changes in the central control of cough and would parallel changes in central ventilatory control assessed by the hypercapnic ventilatory response (HCVR). Twenty-five healthy volunteers underwent measurements of HCVR and citric acid sensitivity at sea level and during a 9 day sojourn at 5200 m. None of the subjects had any evidence of respiratory infection. Citric acid cough threshold felt significantly on ascent to 5200 m. The slope, S, of the HCVR increased significantly on ascent to 5200 m and during the stay at attitude. There was no correlation between citric acid sensitivity and HCVR. We conclude that the change in citric acid cough threshold seen on exposure to hypobaric hypoxia is unlikely to be mediated by changes in the central control of cough. Sensitivity to citric acid may be due to early subclinical pulmonary edema stimulating airway sensory nerve endings. (C) 2009 Elsevier Ltd. All rights reserved.