CO,OC) and the DLCO,RB methods at rest and during exercise (25, 50, and 75% of peak work) in 11 healthy subjects [mean age ϭ 34 yr (SD 11)]. Both DL CO,OC and DLCO,RB increased linearly with cardiac output and external work. There was a good correlation between DL CO,OC and DLCO,RB for rest and exercise (mean of individual r 2 ϭ 0.88, overall r 2 ϭ 0.69, slope ϭ 0.97). DLCO,OC and DLCO,RB were similar at rest and during exercise [e.g., rest ϭ 27.2 (SD 5.8) vs. 29.3 (SD 5.2), and 75% peak work ϭ 44.0 (SD 7.0) vs. 41.2 ml⅐min Ϫ1 ⅐mmHg Ϫ1 (SD 6.7) for DL CO,OC vs. DLCO,RB]. The coefficient of variation for repeat measurements of DL CO,OC was 7.9% at rest and averaged 3.9% during exercise. These data suggest that the DL CO,OC method is a reproducible, well-tolerated alternative for determining DL CO, particularly during exercise. The method is linearly associated with cardiac output, suggesting increased alveolar-capillary recruitment, and values were similar to the traditional rebreathe method.