The primary objective of this study was to test the hypothesis that a catecholamine-dependent mechanism would upregulate alveolar liquid clearance after fluid resuscitation from 15 min of hemorrhagic shock. Anesthetized rats were hemorrhaged to a mean arterial pressure of 35 mmHg for 15 min and were resuscitated with a 4% albumin solution. Alveolar liquid clearance was measured 5 h later by the concentration of protein in the distal airspaces over 1 h after instillation of a 5% albumin solution into one lung. Hemorrhaged rats developed a severe metabolic acidosis that was associated with a significant rise in plasma epinephrine levels throughout the study. There was a 60% increase in alveolar liquid clearance in hemorrhaged and resuscitated rats compared with control rats. Amiloride (10-4 or 10-6 M), propranolol (10-4 M), or bilateral adrenalectomy inhibited the increase in alveolar liquid clearance. This effect was reproduced by the intravenous administration of epinephrine in adrenalectomized and hemorrhaged rats. Thus these data provide evidence for a catecholamine-dependent regulation of sodium transport that protects the airspaces against flooding several hours after fluid resuscitation from hemorrhagic shock.