The adult respiratory distress syndrome (ARDS) is an acute pulmonary disorder characterized by the accumulation of neutrophils within the lower respiratory tract. Because activation of the complement system can generate C5a, a potent neutrophil chemoattractant, complement activation was assessed in both serum and bronchoalveolar lavage fluid obtained from 10 patients with ARDS and compared with that from normal control subjects. Crossed immunoelectrophoresis was used to determine activation of the complement components C3 and properdin factor B (PFB), and radioimmunoassay was used to determine the presence of C5a. Complement activation was not detected either in the plasma or in the lung epithelial lining fluid of the control subjects. In contrast, evidence of C3 activation was found in the plasma of 50% of the patients with ARDS when initially studied; likewise, C3 activation, PFB activation, and C5a could all be detected in the epithelial lining fluid of all patients with ARDS with a single exception. Follow-up bronchoalveolar lavages revealed decreased amounts of C3 activation and C5a 2 to 7 days after the onset of ARDS, and the complement activation had resolved when the patients with ARDS had completely recovered. To determine if the C5a in bronchoalveolar lavage fluid could be responsible for the influx of neutrophils observed in ARDS, epithelial lining fluids obtained from both normal control subjects and from patients with ARDS were fractionated by molecular sieve chromatography. Two distinct fractions of chemotactic activity were found in the ARDS bronchoalveolar lavage fluid.(ABSTRACT TRUNCATED AT 250 WORDS)