Because patients who fail a trial of weaning from mechanical ventilation experience a marked increase in respiratory load, we hypothesized that these patients develop diaphragmatic fatigue. Accordingly, we measured twitch transdiaphragmatic pressure using phrenic nerve stimulation in 11 weaning failure and 8 weaning success patients. Measurements were made before and 30 minutes after spontaneous breathing trials that lasted up to 60 minutes. Twitch transdiaphragmatic pressure was 8.9 +/- 2.2 cm H2O before the trials and 9.4 +/- 2.4 cm H2O after their completion in the weaning failure patients (p = 0.17); the corresponding values in the weaning success patients were 10.3 +/- 1.5 and 11.2 +/- 1.8 cm H2O (p = 0.18). Despite greater load (p = 0.04) and diaphragmatic effort (p = 0.01), the weaning failure patients did not develop low-frequency fatigue probably because of greater recruitment of rib cage and expiratory muscles (p = 0.004) and because clinical signs of distress mandating the reinstitution of mechanical ventilation arose before the development of fatigue. Twitch pressure revealed considerable diaphragmatic weakness in many weaning failure patients. In conclusion, in contrast to our hypothesis, weaning failure was not accompanied by low-frequency fatigue of the diaphragm, although many weaning failure patients displayed diaphragmatic weakness.