Heat and moisture exchangers (HME) are increasingly used to warm and humidify inspired gases in intubated ventilated patients. But these devices add dead space that may alter the alveolar ventilation. This could impair the efficiency of spontaneous ventilation (SV) during weaning trials from mechanical ventilation. Fifteen patients were tested with an HME (Hygrobac-DAR) and a heated humidifier (HH) (Fischer-Paykel MR 450) in a random order during weaning trials in SV with inspiratory pressure support. Minute ventilation VE, tidal volume), and respiratory rate were recorded and arterial blood was sampled for blood gas analysis with each device. The HME gave a significantly greater VE than the HH (9.3 +/- 0.8 L/min vs 8.1 +/- 0.8 L/min; p < 0.005), because of increased respiratory rate (21 +/- 2/min vs 19 +/- 2/min; p < 0.05). Tidal volume was unchanged for HME and HH (470 +/- 32 mL vs 458 +/- 39 mL). The higher PaCO2 with HME than with HH (44 +/- 2 mm Hg vs 42 +/- 2 mm Hg; p < 0.005) revealed an insufficient alveolar ventilation response to the increase in dead space. Arterial Po2 rose with the HME, but not significantly above the HH values (103 +/- 6 mm Hg vs 97 +/- 6 mm Hg; p = 0.055), possibly because of a positive end-expiratory pressure effect of the HME. The need to increase VE in SV when an HME is used should be taken into account during difficult weaning from mechanical ventilation.