After a patient died of anastomotic necrosis following a tracheal resection for the management of recurrent thyroid cancer invading the trachea, which had been treated 6 years previously by thyroid lobectomy and 4,800 cGy of radiation to control known residual disease, we explored methods to promote the healing of tissues damaged by irradiation. Between 1979 and 1992, 22 patients underwent major airway resection and reconstruction after receiving large doses of radiation. The average dose was 4,979 +/- 1,113 cGy (range, 3,150 to 6,840 cGy); the number of fractions, 20 to 38; and the average dose per fraction, 180 cGy (range, 150 to 200 cGy). The interval between irradiation and surgical treatment was 42 +/- 105 months (range, 1 to 480 months). Seven cervical, eight midtracheal, and five carinal resections were performed, as well as two mainstem sleeve resections. Omentum was used to protect the anastomosis in 15 patients (68%), a pericardial fat pad was used in 2, and pleura was used in 2. In 3 patients, sternohyoid muscle was placed between the anastomosis and a major vascular structure, but without a tissue wrap. Two patients (9.0%) died postoperatively. Anastomotic dehiscence was the cause of death in a patient treated for lymphoma, and adult respiratory distress syndrome was the cause in the other patient; this patient had undergone carinal pneumonectomy. Complications developed in 8 patients (36%). Two cervical dehiscences were treated by T-tube placement, 2 patients suffered wound infection, and 1 patient each suffered a myocardial infarction, dysphagia, hemoptysis, and bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)