We sought to determine the normocapnic values of expiratory tidal volume measured by hot-wire anemometer, and to evaluate how often expiratory tidal volume exceeds estimated anatomical dead space during high-frequency oscillatory ventilation (HFOV) in preterm infants. We also sought to determine the relationship between expiratory tidal volume and other respiratory parameters. The neonatal respiration monitor SLE 2100 VPM, a hot-wire anemometer, was used to measure expired tidal volume (V(T,E)) in patients ventilated by the Sensormedics 3,100A during routine clinical use of HFOV. Two hundred and fourteen simultaneous measurements of PaCO(2), V(T,E), fraction of inspired oxygen (FiO(2)), continuous distending pressure (CDP), frequency, and amplitude were obtained from 28 patients. The median birth weight was 852 g (range, 435-3,450 g), and median gestational age was 27.2 weeks (range, 23.3-41.0 weeks). One hundred and eighteen (55%) normocapnic measurements, 42 (20%) hypocapnic measurements, and 54 (25%) hypercapnic measurements were recorded in which the median V(T,E) was 1.67 ml/kg (95% confidence interval (CI), 1.55-1.79), 1.94 ml/kg (95% CI, 1.74-2.14), and 1.54 ml/kg (95% CI, 1.42-1.66), respectively. The measured V(T,E) exceeded 2.0 ml/kg in 30 instances of normocapnic V(T,E) (14%) and 54 of all V(T,E) (25%), and 3 ml/kg only in 7 (3%) and 11 (5%) instances of normocapnic and all V(T,E). There was a significant difference in median normocapnic V(T,E) obtained when FiO(2) was between 0.21-0.35, compared to values obtained when FiO(2) was 0.36-1.0 (1.61 ml/kg (95% CI, 1.52-1.70) vs. 2.06 ml/kg (95% CI, 1.93-2.19), P < 0.002). The calculated values of PaCO(2) between 35-47, using the calculated regression equation for prediction of PaCO(2) (mmHg), correctly predicted normocapnic values in 60% of measurements. Values >47 should predict hypercapnia in 81% of cases. In conclusion, expired tidal volume measurement by heated double-wire anemometer sensor is feasible, provides useful real-time information about tidal volume changes, and may improve the clinical management of HFOV.