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Thirty supine adult patients undergoing general anesthesia for operations on the periphery or lower abdomen were studied to determine the relative merits of mechanical ventilation with a small tidal volume, a small tidal volume with continuous positive pressure, and a large tidal volume. Alveolararterial oxygen tension difference (A-aDo2) improved when continuous positive pressure or large-tidal-volume ventilation replaced small tidal volumes, and when large-tidal-volume ventilation replaced continuous positive-pressure ventilation with a small tidal volume. The largest changes in A-aDo2 occurred in obese patients and in those with high mean A-aDo2's. A small overall improvement in A-aDo2 was noted with time, regardless of the order of delivery of ventilatory patterns. VD/VT was greatest when positive end-expiratory pressure was applied and lowest with large-tidal-volume ventilation. Static lung compliance was highest with large-tidal-volume ventilation. These findings suggest that optimum pulmonary gas exchange in the supine position is produced by large-tidal-volume ventilation.