We developed a simple flow-through system for measuring the net rate of pulmonary excretion of CO2 (VCO2). Its components, connected in series by plastic tubing, are the following: plastic oxygen hood, suction flask used both as a mixing and sampling chamber, Brooks mass flow controller, and wall suction. Gas aliquots withdrawn from the sampling flask are analyzed for CO2 concentration in the laboratory. The system was validated by measuring over a 60-min period the evolution of CO2 from the reaction of sodium carbonate with phosphoric acid. In 9 trials, the mean recovery of CO2 was 99.8%. In 14 studies in 11 preterm infants, we evaluated the reproducibility of duplicate measurements of CO2 production on consecutive days; in 9 of the studies, the coefficient of variation was < 5%, but in other 5 studies, it ranged from 7.7 to 35.8%. We believe that this device might have both research and clinical applicability.