• An experimental model of human onchocercal keratitis was produced by injecting guinea pigs subconjunctivally with microfilariae (Mf) of Onchocerca lienalis. Actively motile O lienalis Mf spontaneously penetrated the central cornea and produced gray-white midstromal opacities, 0.2 to 0.4 mm in diameter, resembling those of human onchocercal punctate keratitis. Histologically, small foci of eosinophil and mononuclear cell infiltration associated with small pockets of interstitial edema were present in the central corneal stroma, with eosinophil infiltrates in the conjunctiva, episclera, limbus, and ciliary body. The severity of the punctate keratitis was increased by repeated subconjunctival inoculations of Mf. Punctate lesions were not seen following subconjunctival injection of Mf in animals previously hyperimmunized by three subcutaneous injections of Mf. Hyperimmunization may produce an immune response capable of destroying the subconjunctivally injected Mf and preventing their migration into the central cornea.