Asthma is a disease characterized by intermittent airway obstruction, inflammatory cell infiltrates, increased mucus production, lung epithelial remodeling, and airway hyperreactivity. The genetics of asthma, as investigated in animal models, is poorly understood. Because no animal model of asthma mimics all of the pathologic and physiological features of asthma, genetic studies have focused on several phenotypes, including intrinsic or native airway hyperreactivity. It is generally accepted that both genetic and environmental factors determine the phenotypic expression of this complex disease. The genetics of airway hyperresponsiveness, as investigated in the mouse, are presented in this review. The inbred mouse currently represents the most valuable genetic resource for understanding the factors that control this complex phenotype.