Several unsaturated fatty acids are precursors of prostaglandins and leukotrienes. Depending on their precursor, these prostaglandins and leukotrienes have different biological characteristics. The effects of topically administered fatty acids on an experimentally provoked inflammatory keratitis were studied in rabbits. Intrastromal injection with human serum albumin induced in the cornea a ring-shaped infiltration with leukocytes, corneal edema and neovascularization. Arachidonic,γ-linoienic, dihomo-γ-linolenic (DHGL), eicosapentaenoic (EPA) and columbinic acid were given as eye drops in a suspension in hydroxypropylmethylcellulose 0.5% three times daily during the experiment. EPA, DHGL, columbinic, andγ-linolenic, but not arachidonic acid, showed a significant inhibition of either leukocyte infiltration, edema or neovascularization. The inhibitory effects of these fatty acids may be caused by topical inhibition of the formation of prostaglandins and leukotrienes in the arachidonic acid cascade in the rabbit cornea.