New equipment designed for the routine measurement of oxygen uptake (VO2) using a closed circuit method has been validated by comparing it with a standard Douglas bag method. The equipment (The Caloric Measurement Unit, CMU) has been tested in 10 critically ill patients during mechanical ventilation (MV) and in 10 spontaneously breathing healthy subjects. Determinations of VO2 and of the resting energy expenditure (REE) were measured in duplicate with the standard method and once with the CMU. Six additional patients receiving MV were studied with the CMU to evaluate the reproducibility and the effect of FIO2 = 1 vs FIO2 = 0.43 on VO2 measurements. Considering the whole group of 10 patients and 10 subjects, the mean difference of VO2 between both methods was -2 +/- 21 ml/min (95% confidence interval, -11.8 to 7.8 ml/min, p = 0.6) standard deviation. Both methods had a similar reproducibility and the mean difference of VO2 measured at the two different FIO2 with the CMU was -3.2 +/- 11 ml/min (95% confidence interval, -14.7 to 8.4 ml/min, p = 0.5). No statistically significant difference was found between derived REE values obtained from either method. These data show a good correlation between the two methods suggesting that CMU may be used in place of the standard method with the same accuracy in measurement of VO2 even at FIO2 = 1.