Local immunological injury caused by acute lung rejection leads to fibroblast proliferation. Hyaluronate is a product of activated fibroblasts and possibly an indicator of fibroblast proliferation. One hundred thirty-six bronchoalveolar lavage and plasma hyaluronate assays were performed in 57 lung transplant recipients. Pulmonary endothelial cell function was assessed by measuring bronchoalveolar lavage levels of purine nucleoside phosphorylase. Presence of acute cellular rejection was monitored by transbronchial biopsy histologic evaluation and was classified as minimal to mild (acute rejection I, II) and moderate to severe (acute rejection III, IV). Infection was confirmed by bronchoalveolar lavage culture and antibiotic sensitivity. Bronchoalveolar lavage hyaluronate levels in clinically stable recipients were 33.5 +/- 4.69 micrograms/L and were significantly higher than with clinically stable recipients (p = 0.0001), infection (p = 0.008), or mild rejection (p = 0.001). Levels were highest in recipients with diffuse alveolar damage (392.4 +/- 60.6 micrograms/L). Diffuse alveolar damage also resulted in significant elevations of plasma HA as compared with stable recipients (p = 0.001) and mild rejection. We conclude that clinically significant injury to the allograft from rejection or diffuse alveolar damage can be assessed by bronchoalveolar lavage hyaluronate assays and suggest that the source of hyaluronate in these instances are activated fibroblasts.