Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology characterized by inflammation of the lower respiratory tract and injury and fibrosis of the lung parenchyma. Neutrophils are a significant component of the alveolitis of IPF, and are known to have a potent armamentarium of mediators capable of damaging the lung parenchyma. To evaluate the ability of 2 pharmacologic agents, corticosteroids and cyclophosphamide, to suppress the neutrophil component of the inflammation of IPF, bronchoalveolar lavage was used to monitor those patients with active disease (greater than 10% neutrophils recovered by lavage). Those patients treated with corticosteroids alone showed no suppression in the neutrophil component of the alveolitis after 3 months and at 6 months of therapy (p greater than 0.8, both compared to before therapy). In marked contrast, patients treated with cyclophosphamide, alone or with corticosteroids, showed a significant reduction in the neutrophil alveolitis at 3 months (cyclophosphamide alone, p less than 0.01; cyclophosphamide and corticosteroids, p less than 0.02; both compared to before therapy) and at 6 months (cyclophosphamide alone, p less than 0.01; compared to before therapy). Pulmonary function tests at the beginning and end of the study were not different in any of the treatment groups. Thus, cyclophosphamide, alone or in combination with corticosteroids, is much more effective than corticosteroids alone in suppressing the neutrophil component of the inflammation of IPF. Whether or not this effect of cyclophosphamide will result in overall stabilization or improvement of the disease will require a larger, likely multicenter, trial.