Certain dietary oils may have therapeutic potential in the treatment of inflammatory skin disorders. Presumably, the fatty acid constituents of these dietary oils exert their effects by altering the levels of cutaneous eicosanoids. Prompted by this possibility, we investigated whether supplementation of guinea pig diets with fish oil [rich in 20:5(n-3)] or borage oil [rich in 18:3(n-6)] could significantly alter epidermal levels of eicosanoids compared with control animals supplemented with olive oil. After feeding periods of 4, 8 or 12 wk, the epidermis from the animals was analyzed for: 1) fatty acid composition of individual epidermal phospholipids, 2) levels of lipoxygenase products, and 3) levels of cyclooxygenase products (prostaglandins). Our results demonstrated that the animals supplemented with dietary fish oil had elevated levels of 20:5(n-3) in epidermal phospholipids and elevated epidermal levels of 15-hydroxyeicosapentaenoic acid (15-HEPE) [the 15-lipoxygenase product of 20:5(n-3)] compared with guinea pigs fed olive oil or borage oil. Similarly, the animals supplemented with dietary borage oil had elevated levels of 20:3(n-6) [the epidermal elongase product of 18:3(n-6)] in epidermal phospholipids and elevated epidermal levels of 15-hydroxyeicosatrienoic acid [15-HETrE, the epidermal 15-lipoxygenase product of 20:3(n-6)] compared with guinea pigs fed olive oil or fish body oil. There were no significant changes in epidermal levels of prostaglandins. Both 15-HEPE and 15-HETrE have been identified as possible anti-inflammatory metabolites, and their elevated presence in the epidermis of animals fed oils rich in 20:5(n-3) or 18:3(n-6) may provide a mechanism for the beneficial effects of these oils on inflammatory conditions.