Patients with tracheal or major airway obstruction owing to inoperable carcinomas are at risk of developing respiratory failure or postobstructive pneumonia. In such cases, there is an urgency to restore the airway. Bronchoscopic interventional procedures for palliation of malignant airway obstruction are becoming more common in clinical practice. However, as current interventional methods may be unavailable or are contraindicated, we have investigated the use of direct intratumoural injection with 5-fluorouracil for tumour regression to open the airway. in this study, 65 patients who presented with greater than 50% obstruction of at least one major airway were treated with 5-fluorouracil injection directly into the endobronchial tumour or area of infiltrated bronchial mucosa through a flexible fiber-optic bronchoscope. The pretreatment luminal opening for this cohort of 65 patients ranged from 0% (totally obstructed) to 40%, with an overall mean luminal opening of 22% (78% occlusion). There was a positive response to intratumoural injection in 56 of 65 patients, and a large reduction in the size of tumours by endoscopic evaluation in the majority of cases. Overall, the mean pretreatment luminal opening of 22.0% was significantly improved to a mean post-treatment luminal opening of 58.5%, an increase in the opening of the airways of 36.5%. The increase in the diameter of the airway lumen was more than 50% for 34 of 65 patients, and 23 showed a 25-50% improvement. The results were of obvious immediate clinical benefit. Statistical analysis of all patient data by a Wilcoxon matched-pairs/sign-ranked test confirmed the significant benefit achieved (P<0.001). The therapy was well tolerated, with no systemic side-effects or any serious complications. The results of this study suggest that in patients with life-threatening airway obstruction, intratumoural injection of anticancer drugs should be regarded as an important new therapeutic approach and an integral part of interventional bronchoscopic management. This study further encourages more general consideration of intratumoural drug injection as a minimally invasive therapeutic method for the treatment of lung cancer and various inoperable cancers.