Thoracic irradiation may cause an acute lymphocytic alveolitis or hypersensitivity pneumonitis. It is well known that cough reflex is sensitized by a number of inflammatory mediators. The purpose of the present study was to investigate the effect of the thoracic irradiation on the cough response in awake guinea pigs. Guinea pigs (Trik strain) were exposed to sham irradiation (n=16), a single irradiation dose of 10 Gy (n=12), and a fractionated irradiation dose (in five fractions) of 15 Gy (n=12) delivered to the thorax. Cough was induced by citric acid aerosol inhalation in gradually increasing concentrations (0.05-1.6 M) during the first week after thoracic irradiation. The cough response was expressed as a total number of coughs induced during all citric acid challenges. Irradiated animals with single dose of 10 Gy exhibited a time- dependent significant increase of citric acid-induced cough in the 6th day after irradiation compared with control animals (P=0.005), whereas cough was not altered significantly in irradiated animals with fractionated dose of 15 Gy. This study demonstrates that the increased cough response may be a determinant of the functional changes of airway nerve-endings mediating cough in the early phase after thoracic irradiation.