Data summarized in this review indicate that airway smooth muscle cells express receptors for cytokines derived from CD4+ T cells and that these cytokines, particularly interleukin-13, can act directly on airway smooth muscle cells leading to changes in contractile and relaxant responses, proliferation, and the ability of smooth muscle cells to generate chemokines such as eotaxin and TARC. Moreover, the interleukin-4 receptor-alpha genotype of airway smooth muscle appears to be an important determinant of its response to Th2 cytokines. Understanding the mechanistic basis for the interactions between these cytokines and airway smooth muscle might suggest new avenues for therapeutic intervention in asthma.