ß-Adrenergic agonists accelerate the clearance of alveolar fluid by increasing the expression and activity of epithelial solute transport proteins such as amiloride-sensitive epithelial Na⁺ channels (ENaC) and Na, K-ATPases. Here we report that adenoviral-mediated overexpression of a human ß₂-adrenergic receptor (ß₂AR) cDNA increases ß₂AR mRNA, membrane-bound receptor protein expression, and receptor function (procaterol-induced cAMP production) in human lung epithelial cells (A549). Receptor overexpression was associated with increased catecholamine (procaterol)-responsive active Na⁺ transport and increased abundance of Na, K-ATPases in the basolateral cell membrane. ß₂AR gene transfer to the alveolar epithelium of normal rats improved membrane-bound ß₂AR expression and function and increased levels of ENaC ( subunit) abundance and Na, K-ATPases activity in apical and basolateral cell membrane fractions isolated from the peripheral lung, respectively. Alveolar fluid clearance (AFC), an index of active Na⁺ transport, in ß₂AR overexpressing rats was up to 100% greater than sham-infected controls and rats infected with an adenovirus that expresses no cDNA. The addition of the ß₂AR-specific agonist procaterol to ß₂AR overexpressing lungs did not increase AFC further. AFC in ß₂AR overexpressing lungs from adrenalectomized or propranolol-treated rats revealed clearance rates that were the same or less than normal, untreated, sham-infected controls. These experiments indicate that alveolar ß₂AR overexpression improves ß₂AR function and maximally upregulates ß-agonist--responsive active Na⁺ transport by improving responsiveness to endogenous catecholamines. These studies suggest upregulation of ß₂AR function may someday prove useful for the treatment of pulmonary edema.