Fibrosing alveolitis may occur alone (CFA) or in association with systemic sclerosis (FASSc). FASSc was recently shown to have a prognostic advantage over CFA. Because interleukin-8 (IL-8) is likely to be a major determinant of neutrophil alveolitis, we evaluated IL-8 expression in patients with CFA and FASSc and compared it with that in normal individuals and sarcoidosis and systemic sclerosis patients without pulmonary involvement (SSc no FA). IL-8 protein in bronchoalveolar lavage fluid (BALF) was assessed by immunoassay, and IL-8 mRNA expression was assessed using Northern analysis and reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization of lung parenchyma. Compared with normal subjects, IL-8 concentration was significantly greater in both CFA (p < 0.001) and FASSc groups (p < 0.05) but no different in sarcoidosis. The IL-8 concentration in CFA was higher than in FASSc (p < 0.01) and was related to BAL % neutrophils (rs = 0.48, p < 0.01). IL-8 mRNA expression evaluated by Northern analysis was seen only in patients with CFA and FASSc and was related to BAL % neutrophils (rs = 0.63, p < 0.01). We suggest that IL-8 is a key factor in the pathogenesis of fibrosing alveolitis and that the poorer prognosis of CFA compared with FASSc is related to higher levels of IL-8 within the lower respiratory tract.