Ocular immunopathologic responses of inbred guinea pigs infected with Onchocerca microfilariae from domesticated animals were studied as a laboratory model of human ocular onchocerciasis. A single intracorneal infection of normal guinea pigs with microfilariae produced only minimal ocular lesions. In contrast, intracorneal infection of guinea pigs previously immunized by systemic infection with microfilariae produced intense corneal and uveal inflammation. Transfer of splenic lymphocytes from immunized donors to syngeneic normal recipients substituted effectively for the active immunization. Cell recipients produced marked corneal inflammatory reactions when challenged by a single intracorneal infection. Fresh and cryopreserved microfilariae produced identical reactions. The corneal inflammatory infiltrates were composed primarily of eosinophils, neutrophils, and plasma cells and resembled human onchocercal keratitis. Diethylcarbamazine citrate administration after a challenge intracorneal infection increased the severity of the corneal inflammatory response in immunized animals.