Recent uncontrolled studies have suggested improved maximal exercise capacity and decreased exercise ventilation in heart failure after administration of increased inspired oxygen concentrations. To study the responses further, 16 patients performed staged, symptom-limited cycle ergometry with humidified 21% and 60% inspired oxygen concentrations using a randomized, double-blind, crossover study design. Serial measurements of minute ventilation, heart rate, blood pressure, leg blood flow, and arterial and venous lactate and oxygen content were obtained. Exercise time did not change between the 2 tests (595 +/- 179 seconds and 602 +/- 181 seconds for 21% and 60% oxygen concentrations, respectively). Similarly, measurements of the ventilatory response to exercise and of leg blood flow were not different between the 2 oxygen concentrations. Although hemoglobin oxygen saturation increased from 96.7 +/- 2.1% to 97.9 +/- 1.5% at rest, at both rest and maximal exercise there was no statistically significant difference in arterial or venous oxygen content. This study failed to demonstrate any physiologic or functional benefit from the administration of increased oxygen concentrations to patients with stable heart failure.