Inhalation of high concentration of oxygen produces oxidative stress in men and experimental animals. Our previous experiments showed that the cough reflex is suppressed in guinea pigs after exposure to 100% O(2) for 60 hours. The aim of this study was to determine the effects of dietary antioxidant supplementation with vitamins C and E on hyperoxia-induced oxidative stress in airway and lung tissues directed on cough reflex. The experimental group (T-H, n=8) was pretreated with vitamins C (500 mg/kg) and E (300 mg/kg) for 4 weeks and subsequently exposed to 100% O(2) for 60 hours. Hyperoxic group (H, n=8) received saline instead of antioxidants and then inhaled 100% O(2) for 60 hours. Cough was induced by inhalation of citric acid aerosol in gradually increased concentration (0.05-1.6 M) at the end of antioxidant therapy and then at the end of exposure to 100% O(2). Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anaesthetized animals just 1 hour after the end of oxygen exposure. Our results showed a tendency to a decrease in citric acid-induced cough in hyperoxic animals and an increase in animals with antioxidant therapy after hyperoxia. Antioxidant therapy significantly unblocked hyperoxia-induced down-regulation of cough (P=0.004). Significant changes also were obtained from mechanically-induced TBr cough [2.5(1-4) vs. 1.0(1-2); P<0.01] between the experimental and hyperoxic (control) animals. In conclusion, our results indicate a protective effect of antioxidant supplementation on oxidant-mediated cough depression.