Activation of -adrenergic receptors in the lung is an important mechanism that can prevent alveolar flooding after brief but severe hemorrhagic shock. However, a neutrophil-dependent oxidant injury to the alveolar epithelium prevents the normal upregulation of alveolar fluid clearance by catecholamines after prolonged hemorrhagic shock. Because hemorrhage increases proinflammatory cytokine expression in the lung partly through the activation of -adrenergic receptors, the objective of this study was to determine whether -adrenergic blockade would restore the normal fluid transport capacity of the alveolar epithelium after hemorrhagic shock. Hemorrhagic shock was associated with a significant increase of interleukin-1 (IL-1) concentration in the lung and a failure of the alveolar epithelium to respond to -adrenergic agonists, with the upregulation of vectorial fluid transport despite intra-alveolar administration of exogenous catecholamines. In contrast, catecholamine-mediated upregulation of alveolar liquid clearance was restored by pretreatment with phentolamine, an -adrenergic-receptor antagonist. Phentolamine pretreatment also significantly attenuated the shock-mediated increase of IL-1 concentration in the lung. Additional experiments demonstrated that the inhibition of IL-1 binding to its receptor by the administration of IL-1-receptor antagonist restored the normal fluid transport capacity of the alveolar epithelium after hemorrhagic shock. In summary, the results of these studies indicate that the activation of -adrenergic receptors after hemorrhagic shock prevents the -adrenergic-dependent upregulation of alveolar fluid clearance by modulating the severity of the pulmonary inflammatory response.