BACKGROUND: The differential diagnosis of bilateral lung infiltrates and prognosis prediction can be challenging for clinicians in the intensive care unit (ICU). We analysed the proteome from bronchoalveolar lavage fluid (BALF) and determined its usefulness for evaluating the infectious causes and mortality associated with bilateral lung infiltrates. METHODS: In the ICU cohort, 136 patients with bilateral infiltrate on chest radiographs were selected, and bronchoscopy with bronchoalveolar lavage (BAL) was performed. Proteomic profiling of the exosomes in the BALF (n=20) was conducted to identify candidate protein biomarkers potentially associated with infection or mortality. The BAL samples (n=116) were used to measure the candidate biomarker levels. RESULTS: The candidate biomarkers, CD20, CLIC4, SCFD1 and TAP1, were selected for the differential diagnosis of infection or mortality. The levels of CD20 were significantly elevated in patients with non-infectious causes, compared with those with infectious causes (248.6±154.5 CONCLUSIONS: Our results suggest that CD20 levels in BALF might be a useful biomarker for differentiating non-infectious and infectious diseases in patients with bilateral lung infiltrates.