Previous studies have indicated that the doubly labeled water method can be used to measure energy expenditure in free-living humans. In this study, we compare the doubly labeled water method with nearly continuous respiratory gas exchange in five healthy adults. Total body water and isotope elimination rates were determined by mass spectrometric analysis of urinary water after the administration of 2H2 18O. Respiratory gas exchange was measured 22 to 23 h/day for 5 consecutive days. Energy expenditures from the doubly labeled water method averaged 6% more than those from respiratory gas exchange with an 8% coefficient of variation.