Bronchopleural fistula (BPF), or bronchopleural air leak, is regarded as an ominous complication of ventilator management in acute respiratory failure, but data on its natural course and prognosis are lacking. We reviewed all instances of mechanical ventilation at a major trauma center during a four-year period, and found that 39 of the 1,700 mechanically-ventilated patients developed BPF lasting at least 24 hrs. Overall mortality in these 39 patients was 67 percent, and this was higher when BPF developed late in the illness (16 of 17, or 94 percent, when mean onset was hospital day 13), than when it occurred within 24 hours of admission (ten of 22, or 45 percent, p = 0.002). Survival in patients with chest trauma (12 of 27, 44 percent), most of whom had air leaks on or just after admission, was better than in those with other primary diagnoses (one of 12, 8 percent, p less than 0.005). All eight patients whose maximum air leak exceeded 500 ml per breath died, whereas 13 of 30 with smaller maximum leaks survived (p less than 0.05). Despite leaks as large as 900 ml per breath, however, conventional ventilator adjustments permitted avoidance of severe respiratory acidosis (pH less than 7.30) in all but two patients. We conclude that the occurrence of BPF during mechanical ventilation identifies patients with high mortality, but that unmanageable respiratory acidosis from this complication is rare.