We examined the water retentive properties of hyaluronan because of its reported therapeutic effect in the treatment of dry eye. Hyaluronan dose dependently retarded water loss from a solution kept at constant temperature and humidity. Similarly, water loss was retarded when hyaluronan was placed atop an agar gel. These decreases in water loss were not related to changes in the molecular weight of hyaluronan. Unlike the in vitro models, the evaporation rate from the tears in normal subjects initially increased following the topical application of hyaluronan, and continued a higher rate than with the vehicle. These results suggest that hyaluronan enhances water retention on the corneal surface, and probably increases corneal wettability. Accordingly, hyaluronan eye drops may be useful in the treatment of dry eye.