Obliterative bronchiolitis is the most significant long-term complication of lung and heart-lung transplantation characterized by the rapid development of obstructive airway disease. It is thought to be a manifestation of chronic rejection and has been treated, with limited success, with augmentation of immunosuppression. Early detection of obliterative bronchiolitis and prompt initiation of therapy may result in an improved outcome. The role of transbronchial biopsy has been reported in the diagnosis of acute rejection and infection but not for obliterative bronchiolitis. To study this problem we retrospectively reviewed the transbronchial biopsy results of patients with advanced clinical obliterative bronchiolitis, as defined physiologically. Between January 1, 1988, and December 31, 1991, 46 "sets" of adequate transbronchial biopsy specimens were obtained from 16 patients (15 heart-lung recipients and one double lung recipient). Seven sets of transbronchial biopsy specimens (15.2%) showed obliterative bronchiolitis by pathologic study. In four patients with severe clinical obliterative bronchiolitis, only one transbronchial biopsy specimen of seven (14.3%) showed obliterative bronchiolitis. The pathologic diagnosis of obliterative bronchiolitis was confirmed in three of these patients at the time of autopsy or retransplantation. Twelve patients were still alive at the end of the study period, and all experienced further deterioration of lung function typical for obliterative bronchiolitis. We conclude that the sensitivity of transbronchial biopsy for obliterative bronchiolitis is poor. Possible explanations for these results are explored.