To investigate the acute effect of a hot, humid and ozone-polluted (O(3)) environment on lung inflammation and oxidative tress of runners performing 8 km time trial run. Using a single-blinded randomized design, 10 male athletes (mean[Formula: see text]= 64.4 mlO(2) kg(-1) min(-1), SD = 4.4) took part in a time trial run in four different environmental conditions: 20°C + 50% relative humidity (rh) (Control); 20°C + 50% rh + 0.10 ppm O(3) (Control + O(3)); 31°C + 70% rh (Heat); 31°C + 70% rh + 0.10 ppm O(3) (Heat + O(3)). Blood samples and nasal lavage were collected post-exercise and analyzed for inflammatory, epithelial damage and oxidative stress markers. Data were analyzed using repeated measures ANOVA with Tukey's post hoc test. A significant increase in CC16 concentration (P < 0.05) and GSH/protein concentration (P < 0.05) in the upper respiratory airways was observed following the 8 km run in the Heat + O(3) trial compared with the control trial. There were no differences in the neutrophil counts between trials. No differences were observed for the other antioxidants analyzed. A hot, humid and ozone-polluted environment (0.1 ppm) elicits an early epithelial damage and antioxidant protection process in the upper respiratory airways of athletes immediately after performing 8 km time trial run.