This study investigated the effects of administration of methylprednisolone on oxygen transport in ten stable hypoxemic (mean arterial oxygen pressure, 54 +/- 3 mm Hg) patients with chronic obstructive pulmonary disease (COPD). At 24 hours (after four injections of a bolus of 30 mg of methylprednisolone sodium succinate per kilogram of body weight, given intravenously every six hours), significant differences (P less than 0.05) were an increased cardiac index (3.0 +/- 0.2 to 4.1 +/- 0.2 L/min/sq m), a decreased peripheral vascular resistance (1,186 +/- 100 to 849 +/- 60 dynes/sec/cm-5), an increased flow of oxygen to tissue (0.90 +/- 0.07 to 1.16 +/- 0.09 L/min), a decreased arteriovenous oxygen content difference (49 +/- 3 to 43 +/- 2 ml/L), a decreased concentration of hydrogen ions in the arterial blood (38 +/- 1 to 35 +/- 1 nmol/L) and arterial carbon dioxide tension (39 +/- 2 to 32 +/- 1 mm Hg), and increased levels of lactate (1.1 +/- 0.2 to 3.7 +/- 1.0 mmol/L) and pyruvate (0.14 +/- 0.04 to 0.37 +/- 0.08 mmol/L). Fractional oxygen utilization, oxygen consumption, the partial pressure of oxygen at which hemoglobin was 50 percent saturated, and the level of 2,3-diphosphoglyceric acid remained unchanged. In vitro studies showed that these patients' red blood cells responded with a significant (more than 35 percent) increase in the level of 2.3-diphosphoglyceric acid when incubated for ten hours with concentrations of methylprednisolone that were much higher (1.0 mg/ml) than those attained in vivo (12.5 microgram/ml). These studies demonstrate that repeated infusions of high doses of steroids in a bolus in stable hypoxemic patients with COPD produce significant physiologic changes but no apparent net gain in the oxygenation of tissues.