Large room calorimeters are capable of rapid measurements that are usually made in hoods or small rooms. We evaluated the performance gains of four calorimeters constructed with modern control systems, sample gas preparation and data processing. Calibration of the calorimeters and instruments was performed in place, with traceability to international standards. Performance was evaluated by infusion of N2-CO2 gas and 243 24-h studies of individuals. Our subjects included children weighing 20 kg and adults engaged in heavy exercise. Errors for 24-h infusion measurements (n = 23) were -0.34 +/- 1.24% for oxygen consumption rate and 0.11 +/- 0.98% for carbon dioxide production rate. Calorimeter 90% response times were 2 to 6 min over a range of oxygen consumption rates from 100 to > 4000 mL/min. Closed-loop control of supply and exhaust air flows provided consistent 24-h mean CO2 levels (0.39 +/- 0.015%) and pressures (13.2 +/- 4.4 Pa). Room calorimeters operated with closed-loop control can be used for accurate measurement of energy expenditure rate dynamics for a wide range of individuals.