The use of a multiple gas rebreathing method for the measurement of cardiopulmonary function in mechanically ventilated neonates was evaluated. The following indices of cardiopulmonary function were assessed in 20 piglets (mean weight, 2.3 kg): (1) pulmonary capillary blood flow (Q), (2) diffusing capacity for carbon monoxide (DLCO), (3) lung gas volume (FRC), (4) oxygen consumption (VO2), and (5) volume of the pulmonary tissues and capillaries (VTPC), the latter an estimate of total lung water. During mechanical ventilation at zero end expiratory pressure, all rebreathing parameters correlated well with body weight. Additionally, a good correlation (r = 0.81, slope = 0.99) between VTPC and postmortem estimate of total lung water was observed. The effect of ventilation with positive end expiratory pressure (PEEP) was then studied in 10 piglets.