During hydrostatic pulmonary edema, active Na⁺ transport and alveolar fluid reabsorption are decreased. Dopamine (DA) and isoproterenol (ISO) have been shown to increase active Na⁺ transport in rat lungs by upregulating Na⁺-K⁺-ATPase in the alveolar epithelium. We studied the effects of DA and ISO in isolated rat lungs with increased left atrial pressure (Pla = 15 cmH₂O) compared with control rats with normal Pla (Pla = 0). Alveolar fluid reabsorption decreased from control value of 0.51 ± 0.02 to 0.27 ± 0.02 ml/h when Pla was increased to 15 cmH₂O (P < 0.001). DA and ISO increased the alveolar fluid reabsorption back to control levels. Treatment with the D₁antagonist SCH-23390 inhibited the stimulatory effects of DA (0.30 ± 0.02 ml/h), whereas fenoldopam, a specific D₁-receptor agonist, increased alveolar fluid reabsorption in rats exposed to Pla of 15 cmH₂O (0.47 ± 0.04 ml/h). Propranolol, a β-adrenergic-receptor antagonist, blocked the stimulatory effects of ISO; however, it did not affect alveolar fluid reabsorption in control or DA-treated rats. Amiloride (a Na⁺ channel blocker) and ouabain (a Na⁺-K⁺-ATPase inhibitor), either alone or together, inhibited the stimulatory effects of DA. Colchicine, which disrupts the cellular microtubular transport of ion-transporting proteins to the plasma membrane, inhibited the stimulatory effects of DA, whereas the isomer β-lumicolchicine did not block the stimulatory effects of DA. These data suggest that DA and ISO increase alveolar fluid reabsorption in a model of increased Pla by regulating active Na⁺ transport in rat alveolar epithelium. The effects of DA and ISO are mediated by the activation of dopaminergic D₁receptors and the β-adrenergic receptors, respectively.