Oxygen uptake (VO2) and exercise efficiency during cycle ergometer exercise are considered to be independent of body mass. To determine the validity of this assumption, 50 females ranging in body mass from 41.5-98.9 kg exercised on a cycle ergometer with no load at 60 rpm and at 25, 50, 75, and 100 W at 60 and 90 rpm. Gross VO2 and efficiency, net VO2 and efficiency, work VO2 and efficiency, and delta efficiency were computed. Gross and net VO2 were significantly and positively correlated with body mass at all work rates and pedal frequencies. Gross efficiency was significantly and negatively correlated with body mass at all work rates and pedal frequencies. Work VO2 and body mass were not significantly correlated. The correlations between work and delta efficiency and body mass were not significant. Since body mass was found to be significantly correlated with gross VO2, the following equation was developed using stepwise multiple regression to predict gross VO2: VO2 (ml.min-1) = 10.9 (work rate, W) + 8.2 (pedal rate, rpm) + 8.3 (body mass, kg) - 559.6. These data suggest that body mass should be considered when estimating the oxygen uptake during cycle ergometer exercise.