We used inspiratory resistive training (IRT) in an effort to improve the respiratory muscle endurance of 27 patients with respiratory failure who had failed repeated weaning attempts using standard techniques. Seven patients had primary neuromuscular diseases; the other 20 had primary lung diseases. All patients had stable respiratory failure, without gross malnutrition or electrolyte disorders. Their best initial T-piece duration averaged 6.4 +/- 8.4 (SD) h, with pHa 7.33 +/- 0.09 and PCO2 63 +/- 4 torr at the end of the T-piece trial. We provided a mean of five weekly training sessions of spontaneous breathing through an adjustable nonlinear resistor, with gradually increasing duration and resistance. When initial T-piece tolerance was less than 2 h, two to ten breaths of mechanical ventilation were provided during IRT sessions. No training session exceeded 30 min, and mechanical ventilation was provided between IRT sessions. Under this regimen, maximal inspiratory pressure improved from -37 +/- 15 to -46 +/- 15 cm H2O (p less than .001) and vital capacity improved from 561 +/- 325 to 901 +/- 480 ml (p less than .001). Twelve of the 27 patients were successfully weaned after 10 to 46 days; five more were weaned to nocturnal ventilation, for a total of 63%. We conclude that IRT can improve respiratory muscle strength and endurance in patients with respiratory failure, and can allow many of them to be weaned from mechanical ventilation.