While most attempts at developing a treatment for pulmonary emphysema have focused on the use of elastase inhibitors to reduce elastic fiber damage and the loss of alveoli, this laboratory has developed a method of preventing such injury by the intratracheal administration of hyaluronan (HA). Animals treated with HA prior to the induction of experimental emphysema develop significantly less disease than untreated controls. The protective effect of HA may be related to its ability to bind to lung elastic fibers, thereby preventing their breakdown by elastases. Although clinical trials involving nebulized HA are not expected to yield a measurable treatment effect for at least several years, it is proposed that the special ability of this polysaccharide to retain water may increase the elasticity of lung elastic fibers, producing a relatively rapid improvement in pulmonary mechanics. Such an outcome might speed the development of this potential treatment for pulmonary emphysema.