The alveolar epithelium is the major barrier to solute and protein flux between the pulmonary vascular bed and the airspaces. Hyperoxic exposure increases epithelial permeability, and during recovery, normal permeability must be regained. To determine the time course for recovery of this function, we exposed hamsters to > 95% O2 for 4.5 days and returned them to room air. After recovery periods of 0.5, 1, 3, 7, and 14 days, alveolar epithelial permeability x surface area (PS) values for [14C]sucrose and fluorescein isothiocyanate-Dextran 20 were measured with isolated perfused lung techniques. Eighty-five percent of the exposed animals survived in room air. Control PS values for sucrose and Dextran 20 were 5.76 x 10(-5) and 0.29 x 10(-5) cm3/s, respectively. After hyperoxia both values were increased by a factor of five. After 0.5 days of recovery, PS remained elevated, but after 1 day they were decreased. Normal PS values were achieved after 3 days for sucrose and 7 days for Dextran 20. During both acute injury and recovery, epithelial selectivity was unchanged and no ultrastructural changes in the alveolar epithelium were observed.