Bulky endobronchial tumours in patients with lung cancer are difficult to treat. Brachytherapy and photodynamic therapy (PDT) are variably effective, and the combination of these treatments is not often recommended. However, cell culture studies and animal studies indicate a possible synergistic effect of combining PDT with ionising radiation. We assessed the safety and effectiveness of combined brachytherapy and PDT in patients with bulky endobronchial lung cancer. Patients with histologically proven non-small cell bronchogenic carcinoma and bulky endobronchial tumours were treated using a combination of PDT (Photofrin, 2 mg/kg) and brachytherapy. Six weeks after PDT, brachytherapy was applied with five fractions of 4 Gy at weekly intervals. Follow up was performed with standard and autofluorescence bronchoscopy and tissue biopsies every 3 months. Thirty two patients were treated. Tumours were extensive with lengths ranging from 10 to 60 mm along the bronchus and estimated volumes ranging from 40 to 3500 mm3. At a mean follow up of 24 months, 26 patients were free of residual tumour and local recurrence. The remaining patients received a second treatment with PDT, brachytherapy, Nd:YAG laser coagulation, or external beam radiation. Distant metastases (lung, lymph node) developed in two of the six patients. Currently, all 32 patients are well. There is no evidence of residual or local recurrent endobronchial cancer in 28 patients and none had severe complications. The combination of PDT and brachytherapy for treating patients with lung cancer and extensive endobronchial tumour is safe and, in this study, had excellent therapeutic efficacy.