Hypoxia diminishes alveolar fluid reabsorption by inhibition of Na-reabsorption. Since terbutaline stimulates Na-transport but impairs b2-adrenergic signaling, we tested whether pretreatment with terbutaline prevents hypoxic transport inhibition. Short circuit currents (ISC) were measured primary rat alveolar type II (ATII) cells grown on permeable support in absence and presence of terbutaline in normoxia and hypoxia (1.5% O2; 24h). Control and pretreated cells were stimulated acutely with terbutaline. 24h treatment with terbutaline in normoxia and hypoxia stimulated transport (+25%). Hypoxia decreased the amiloride-sensitive portion of ISC in control cells (-25%) and after 24h-terbutaline-treatment. In hypoxia but not normoxia, 24h terbutaline increased Na/K-ATPase capacity. ENaC-capacity was increased in both oxygenation states (+20%). In normoxia, acute stimulation with terbutaline rapidly decreased ISC (-20%) followed by a slow increase within about 20 min. Cl-depletion abolished the fast transient decrease whereas the slow increase was still seen indicating that terbutaline stimulated a Cl-current followed by an increase in Na-transport. In hypoxia, terbutaline-stimulation induced similar changes, but the initial decrease was less. Terbutaline caused a 4-fold increase in cAMP formation in normoxia, which was decreased by hypoxia (-20%). 24h terbutaline decreased terbutaline-induced cAMP formation -(85%). Our results indicate that, although hypoxia inhibits Cl and Na-transport in primary rat ATII cells, terbutaline stimulates ISC also in hypoxia and even after prolonged pretreatment with terbutaline despite decreased cAMP production. These results indicate that acute and prolonged treatment with b2 adrenergic agents blunts hypoxic transport inhibition and that a small number of residual b2-receptors seem sufficient for stimulation of transport.