Pulmonary fibrosis is a devastating disorder that is resistant to treatment. Patients with idiopathic pulmonary fibrosis (IPF) have a median survival of 4 to 5 yr after onset of symptoms (1). Although corticosteroids continue to be the primary mode of treatment for this disorder, they improve lung function in less than 30 percent of treated patients. Pulmonary fibrosis can also arise from known precipitating factors, including lung exposure to exogenous agents by inhalation, as with pneumoconioses or hypersensitivity pneumonitis, or systemically, as with drug-induced pulmonary fibrosis. One drug, bleomycin, is associated with significant pulmonary side effects, including fibrosis, that can limit its use. Bleomycin was first noted to cause pulmonary fibrosis in initial trials using the drug (2). Since that time, risk factors and incidence of bleomycin-induced pneumonitis/fibrosis have been elucidated (3). Overall, approximately four percent of patients treated with the drug develop pneumonitis and fibrosis. Although prognosis of bleomycin pneumonitis/fibrosis is difficult to quantitate because of the affected patients’ underlying illnesses, it is most likely much better than for patients with IPF. Bleomycin also has well documented subcellular effects on normal and malignant tissues, including the generation of reactive oxygen species (4) and induction of apoptosis (5).

Shortly after pulmonary fibrosis was noted in humans receiving bleomycin, an animal model was developed (6). Subsequently, there has been a wealth of studies employing bleomycin in mice, rats, hamsters, dogs, and other species (5). Although there are some limitations in these animal models, they have generally been helpful in directing research toward the understanding of the mechanisms of pulmonary fibrosis in humans. The limitations of extrapolating animal models of bleomycin-induced pulmonary fibrosis to IPF or bleomycin toxicity in humans include (1) the natural resolution of fibrosis induced by intratracheal