Background: Hand dermatitis is a common therapeutic challenge with limited and unsatisfactory therapy modules. A possible beneficial role of oral evening primrose oil needs to be investigated. Objective: Pharmacological doses of γ-linolenic acid (GLA) could improve the water permeability barrier of the epidermis in chronic hand dermatitis. Clinical improvement, changes in the lipo-gram and epidermal lipid composition could define functional improvement of the skin. Electron-microscopic evaluation of the epidermal lipid bilayer could underline the efficacy of essential fatty acids in chronic hand dermatitis. Methods: Thirty-nine patients with chronic ( > 1 year), stable hand dermatitis entered a 24-week double-blind placebo-controlled trial. Patch test with the European standard of allergens, haematogram and serum IgE values were determined before commencement of the study. Active therapy (600 mg/day of GLA) was administered to half the patient group. Medication was given for 16 weeks and observations continued for another 8 weeks. Patients were assessed clinically, using a visual analogue scale at 4-week intervals. Plasma and red blood cell lipograms, as well as skin biopsies, were taken before therapy, after the 16-week supplementation period and at week 24. Tissue was used for histological evaluation, electron-microscopic assessment and epidermal lipid analysis. Results: Improvement in clinical parameters was present in the Epogam® and placebo groups, but no statistical difference could be confirmed between the groups. Haematogram, blood and epidermal biochemistry were normal at baseline. No change in the lipid composition of plasma red cells or epidermis could be detected during the trial. Ultrastructurally skin specimens showed no change during the study period. Conclusion: The study indicates that the therapeutic value of orally administered GLA for chronic hand dermatitis is not superior to that of placebo.