Smoke-inhalation injury causes a destruction of the ciliated epithelium that lines the tracheobronchial tree. Casts produced from these cells, polymorphonuclear leukocytes and mucus, can cause upper-airway obstruction, contributing to pulmonary failure. We have reported that a combination of aerosolized heparin and a mucolytic agent, N-acetylcystine [corrected], can ameliorate cast formation and reduce pulmonary failure secondary to smoke inhalation. In this study, 90 consecutive pediatric patients between 1985 and 1995 who had bronchoscopically diagnosed inhalation injury requiring ventilatory support were studied. Forty-three children admitted between 1985 and 1989 acted as controls. Forty-seven children admitted between 1990 and 1994 received 5000 units of heparin and 3 ml of a 20% solution of N-acetylcystine [corrected] aerosolized every 4 hours the first 7 days after the injury. All patients were extubated when they were able to maintain spontaneously a PaO2/FIO2 ratio of more than 400. The number of patients requiring reintubation for successive pulmonary failure was recorded, as was mortality. The results indicate a significant decrease in reintubation rates, in incidence of atelectasis, and in mortality for patients treated with the regimen of heparin and N-acetylcystine [corrected] when compared with controls. Heparin/N-acetylcystine [corrected] nebulization in children with massive burn injury and smoke-inhalation injury results in a significant decrease in incidence of reintubation for progressive pulmonary failure and a reduction in mortality.