Many, if not most, of the different cell types within the lung have been shown to express β₂-adrenergic receptors (β₂ARs) on the cell surface. β₂ARs have thus been implicated in the regulation of many aspects of lung function. However, the physiologic and therapeutic relevance for many of these cell-specific responses has been difficult to establish because of confounding effects that result from the simultaneous activation of receptors on multiple cell types in an in vivo environment. It has been recognized in in vitro models that overexpression of G-protein-coupled receptors such as the β₂ARs can increase the number of spontaneously active receptors (R*) and thereby promote autonomous signal transduction or enhanced agonist sensitivity. With transgenic techniques, high levels of receptor expression and activation can also be attained in vivo. By further using cell-specific promoters to direct expression, it is possible to express β₂ARs in select cell types of a heterogeneous organ such as the lung. In this manner, activation of receptor signaling is limited to the targeted cell. Promoter-directed transgenesis can therefore be a useful tool to delineate cell-specific β₂AR-mediated effects in the lung. (J Allergy Clin Immunol 2002;110:S236-41.)