Weaning from controlled ventilation was attempted in 20 patients who were ventilated with volume constant ventilators for at least 24 hours before study. Measurement of alveolar to arterial oxygen tension differences on 100% oxygen (Aa DO2 1.0) in patients who failed to wean (nonweaners, n = 10), showed a mean AaDO21.0 at 5 minutes after beginning to wean of 388 +/- 56 mm Hg (SEM), and right-to-left shunt (QS/Qt) of 21% values which were significantly different from control (p less than 0.025) and significantly different from ten patients who weaned (p less than 0.005). Since rises in QS/Qt were not accompanied by increased pulmonary capillary wedge pressure, the increased QS/Qt was most likely due to acute atelectasis and not left ventricular failure. These data suggest that patients who fail an initial period of weaning should be placed on positive end-expiratory pressure during subsequent weaning attempts. Significant increases in cardiac output and atrial PCO2 occurred in both groups. Assessment of urinary catecholamine excretion during weaning suggests that sympathoadrenal stimulation often is intense and usually is greater in those patients who weaned successfully. Increased arterial PCO2 may be the mechanism for sympathoadrenal stimulation and rises in cardiac output (r = 0.39, p less than 0.01) during weaning.