Oxyhemoglobin affinity was assessed in 20 subjects with chronic obstructive pulmonary disease, all of whom experienced acute respiratory failure. PaCO2, pH, and 2,3-diphosphoglycerate (2,3-DPG) were measured 24 and 48 h after admission, and then during weaning (for the ten patients on mechanical ventilation) or on discharge (for the ten nonventilated patients). At 24 h, nonventilated patients had a lower pH (p less than .001) and 2,3-DPG concentration (p less than .05) and a higher PaCO2 (p less than .01) than ventilated patients; 48 h later only PaCO2 was higher (p less than .01) in the former, and there were no differences between the two groups in the final set of measurements. There was a persistent left shift in the oxyhemoglobin dissociation curve (P50 at pH 7.4) in both groups throughout the study period. In contrast, the in vivo P50 was significantly lower in ventilated patients only at 24 h (22.7 +/- 2.2 vs. 25.8 +/- 1.5 torr, respectively, p less than .005). Our results suggest that changes of in vivo P50 in ventilated patients are probably related to the Bohr effect induced by mechanical ventilation. The latter swiftly corrects severe respiratory acidosis, causing an intra-erythrocytic alkalotic pH and raising the levels of 2,3-DPG.