The effect of topically administered sodium hyaluronate (Na-HA) on the healing of corneal epithelial defect was investigated using rabbit eyes. The corneal epithelium was removed surgically or with iodine vapor or n-heptanol, and saline was administered to one eye as the control, and 0.1% or 0.25% Na-HA with a molecular weight of 87.3 x 10(4) to the other eye once daily. The area of epithelial defect was measured once daily before a topical administration, and the healing rate of epithelial defect was calculated. When the corneal epithelium was removed with iodine vapor, a topical administration of 0.1% or 0.25% Na-HA did not significantly accelerate the epithelial healing. But when removed surgically or with n-heptanol, the healing rates of the corneas treated with 0.25% Na-HA significantly exceeded those of the control eyes. When the epithelium was removed surgically, treatment with 0.1% Na-HA also significantly accelerated the healing. To determine why the effect of Na-HA differed in these three models with the epithelial defect, the amount of fibronectin (FN) produced by the cornea were investigated. The amount of FN produced was determined from the concentration of FN in the medium obtained after incubation of the corneo-scleral section with corneal epithelial defect, and the amount of Na-HA retained on that cornea was estimated from radioactivity detected in tears and cornea after a topical administration of 14C-labeled Na-HA (14C-Na-HA). The corneo-scleral section whose corneal epithelium had been removed surgically, or with n-heptanol, produced a significantly larger amount of FN than that whose corneal epithelium had been removed with iodine vapor. In addition, the amount of 14C-Na-HA retained on the cornea of the first or second model also significantly exceeded that on the cornea of the third model. The topical administration of Na-HA would thus appear to accelerate the healing of the epithelial defect producing a larger amount of FN or retaining a larger amount of Na-HA.