Pulmonary fungal infection is diagnosed in up to 15-25% of lung transplant recipients and frequently bears a fatal outcome. This prospective uncontrolled study addresses the efficacy and safety of pre-emptive azole therapy against fungal infection in these patients. Fluconazole or itraconazole have been systematically used according to reported fungus sensitivity after the discovery of fungi in lower respiratory tract samples. Patients were treated until the bronchial suture was normal and the cultures of the following bronchoscopy remained negative. Fungi were found post-transplantation in the lower respiratory tract specimens of 26 out of 31 (84%) patients, predominantly Candida albicans (20 patients) and Aspergillus fumigatus (16 patients). Mycelia characteristic of Candida spp. or Aspergillus spp. were found in necrotic tissue at the bronchial suture of nine patients. The mean duration of the 38 treatments was 3.6+/-2.6 months (range, 0.5-12 months). After a median follow-up of 16 (range, 0-48) months, two cases of extended ulcerative and pseudo membranous Aspergillus fumigatus bronchitis were observed and healed under itraconazole treatment. In conclusion, pre-emptive azole therapy may be effective and well-tolerated in lung transplant patients where fungi are found in the airways or pleura.