Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with omega-6 (n-6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either gamma-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p < 0.05) increase in plasma dihomo-gamma-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E2 and leukotriene B4). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n-6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n-6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.