After tracheal extubation, upper and total airway resistances may frequently be increased resulting in an increase in inspiratory effort to breathe. We tested whether breathing a helium-oxygen mixture (HeO(2)) would reduce inspiratory effort in the period after extubation. Eighteen consecutive patients with no chronic obstructive pulmonary disease who had received mechanical ventilation (> 48 h) were successively studied immediately after extubation (N(2)O(2)), 15 min after breathing HeO(2), and after return to N(2)O(2). Effort to breathe, assessed by the transdiaphragmatic pressure swings (DeltaPdi) and the pressure-time index of the diaphragm (PTI), comfort, and gas exchange, were the main end points. The mean reduction of the transdiaphragmatic pressure under HeO(2) was 19 +/- 5%. All but three patients presented a decrease in transdiaphragmatic pressure under HeO(2), ranging from - 4 to - 55%, and a significant reduction in DeltaPdi was observed between HeO(2) and N(2)O(2) (10.2 +/- 0.7 versus 8.6 +/- 1.1 versus 10.0 +/- 0.8 cm H(2)O for the three consecutive periods; p < 0.05). PTI also differed significantly between HeO(2) and N(2)O(2) (197 +/- 19 versus 166 +/- 22 versus 201 +/- 23 cm H(2)O/s/min for the three periods; p < 0.05). Breathing HeO(2) significantly improved comfort, whereas gas exchange was not modified. We conclude that the use of HeO(2) in the immediate postextubation period decreases inspiratory effort and improves comfort.