Inhalation of aerosolized low-molecular-weight (150-kDa) hyaluronan (HA) was previously shown by this laboratory to prevent experimentally induced pulmonary emphysema without associated toxicity. Nevertheless, other investigators have found that low-molecular-weight HA may be proinflammatory, prompting the authors to determine if aerosolized HA could possibly enhance pulmonary inflammation in a different model of lung injury involving intratracheal instillation of endotoxin to hamsters. Results indicate that exposure to HA following endotoxin administration significantly increased lung inflammation, whereas pretreatment with HA had the opposite effect.