The purpose of these experiments was to compare the effects of breathing air (79% N2-21% O2) and a normoxic helium oxygen gas mixture (He-O2) (79% He-21% O2) on maximal oxygen uptake (VO2 max) and work tolerance during both incremental and high-intensity constant load exercise. First, eight subjects underwent two separate short incremental cycle ergometer exercise tests until the subject could not maintain the desired power output. Second, four subjects exercised to exhaustion on two separate occasions at a constant exercise intensity (100% VO2 max). Each exercise protocol required the subject to breathe air on one test and a normoxic He-O2 mixture on an additional occasion. Data analysis revealed higher (P less than 0.05) minute ventilations, an increased time to exhaustion, and a greater VO2 max during He-O2 breathing in both exercise conditions. Small but significant (P less than 0.05) differences existed in the percent hemoglobin saturated with O2 (% SO2) at exercise demands greater than 120 W during the incremental experiment and during each minute of the constant load test with He-O2 giving the higher value. These data support the hypothesis that breathing a normoxic He-O2 gas mixture during exercise elevates VO2 max and increases exercise tolerance. Further, although it appears that breathing a He-O2 mixture results in higher %SO2 during intense exercise, the increase in arterial O2 content is small and probably does not fully account for the higher VO2 max observed under these conditions.