One hundred one infants with chronic respiratory failure (CRF) who required prolonged mechanical ventilation were cared for in the pediatric intensive care unit at The Children's Hospital of Philadelphia between January 1967 and December 1984. Chronic respiratory failure of infancy is a condition that requires mechanical ventilation for more than 28 days in the first year of life. Thirty-six children had severe bronchopulmonary dysplasia, 50 had congenital anomalies, and 15 had neuromuscular disorders. The mean duration of mechanical ventilation for the 101 patients was 12.3 months. Seventy-one children were alive, and 53 (75%) of the 71 had been weaned from mechanical ventilation as of Dec 31, 1984. Pulmonary insufficiency and cardiac failure were the predominant causes of death in 17 of 22 infants in the first two years after the onset of CRF; four of eight deaths that occurred beyond two years were caused by airway- and ventilator-related accidents. Mechanical ventilatory support was emphasized for as long as necessary to provide normal blood gas tensions, nutrition, growth, and development rather than weaning as rapidly as possible. This clinical experience demonstrates that it is feasible to save over 70% of infants with the severest forms of CRF and prolonged ventilator dependency.