Athletes who perform repeated exercise while breathing cold air have a high prevalence of asthma-like chronic airway disease, but mechanism linking such activity to airway inflammation is unknown. We used a novel animal model (exercising horses) to test the hypothesis that exercise-induced chronic airway disease is caused by exposure of intrapulmonary airways to unconditioned air, resulting in the upregulation of cytokine expression. Bronchoalveolar lavage fluid (BALF) was obtained from 8 horses 5 h after submaximal exercise while breathing room temperature or subfreezing air in a random crossover design. BALF total and differential nucleated cell counts were determined and relative cytokine mRNA expression in BALF nucleated cells was quantified using real-time RT-PCR using primer and probe sequences specific for equine targets. There were no significant changes in total or differential cell concentrations between BALF recovered after warm and cold air exercise, although there was a strong trend towards increased concentrations of airway epithelial cells after cold air exercise (p = 0.0625). T_H2 cytokines Interleukin (IL)-4, IL-5, and IL-10 were preferentially upregulated after cold air exercise 12, 9, and 10-fold, respectively, compared to warm air exercise. Other cytokines (IL-2 and IL-6) were upregulated to a lesser extent (6 and 3-fold, respectively) or not at all (IL-1, IL-8, Interferon-, and Tumor Necrosis Factor-). These results suggest that cold weather exercise can lead to asthma-like airway disease through the local induction of cytokines typical of the T_H2 phenotype.