Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung characterized by an inflammatory infiltrate, alveolar type II cell hypertrophy and hyperplasia, and ultimate parenchymal scarring. The phospholipid composition of the surface-active material recovered by bronchoalveolar lavage (BAL) is abnormal in this disease. In the present study we have extended the analysis of surfactant components in IPF to include the major surfactant-associated protein, surfactant protein A (SP-A). SP-A has been reported to be essential for the formation of tubular myelin, to facilitate the adsorption of phospholipid to the air/liquid interface, and to stimulate uptake and inhibit secretion of surfactant in vitro. The BAL of 25 normal volunteers and 42 patients with interstitial lung disease (ILD) was analyzed for surfactant protein A content by ELISA and for phospholipids. The changes in BAL components were correlated to histopathologic markers at open-lung biopsy, clinical status, and survival. The total phospholipid (PL) recovered at lavage was reduced in patients with IPF relative to normal volunteers (p < 0.0005). In addition, the percentage of phosphatidylglycerol (% PG) was decreased in patients with IPF (p < 0.0001), whereas the percentage of phosphatidylcholine that was saturated was not altered. The content of surfactant protein A in lavage was reduced, even when normalized for the total amount of surface-active material recovered (SPA/PL) (p < 0.007). The reduction in SP-A was not specific to IPF but also occurred in other interstitial lung diseases. The SP-A/PL ratio at initial lavage correlated both with the course of disease over a 6-month interval as assessed by a clinical-radiographic-physlologic (CRP) scoring system and with mortality. The percentage PG did not correlate with disease progression or with mortality. Although the pathophysiologlc relevance of these surfactant alterations remains to be defined, we conclude that BAL surfactant protein A content is reduced in IPF and can be used to stratify outcome.