Background: Profound changes in the metabolism of eicosanoids with increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Free eicosapentaenoic acid (EPA) may compete with liberated AA and result in an antiinflammatory effect. Objective: Our purpose was to assess the efficacy and safety of intravenously administered fish-oil–derived lipid emulsion on chronic plaque-type psoriasis. Methods: A double-blind, randomized, parallel group study was performed in eight European centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis with a severity score of at least 15 according to the Psoriasis Area and Severity Index (PASI) participated in a 14-day trial. They were randomly allocated to receive daily infusions with either a ω-3 fatty acid–based lipid emulsion (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA); 43 patients) or a conventional ω-6-lipid emulsion (Lipovenous; EPA+DHA < 0.1 gm/100 ml; 40 patients). The groups were well matched with respect to demographic data and psoriasis-specific medical history. Efficacy of therapy was evaluated by changes in PASI, in an overall assessment of psoriasis by the investigator, and a self-assessment by the patient. In one center neutrophil 4- versus 5-series leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were investigated and plasma-free fatty acids were determined. Results: The total PASI score decreased by 11.2 ± 9.8 in the ω-3 group and by 7.5 ± 8.8 in the ω-6 group (p = 0.048). In addition, the ω-3 group was superior to the ω-6 group with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient. Response (defined as decrease in total PASI of at least 50% between admission and last value) was seen in 16 of 43 patients (37%) receiving the ω-3 emulsion and 9 of 40 patients (23%) receiving ω-6 fatty acid–based lipid emulsion. No serious side effects were observed. Within the first few days of ω-3 lipid administration, but not in the ω-6 supplemented patients, a manifold increase in plasma-free EPA concentration, neutrophil leukotriene B₅ and platelet thromboxane B₃ generation occurred. Conclusion: Intravenous ω-3-fatty acid administration is effective in the treatment of chronic plaque-type psoriasis. This effect may be related to changes in inflammatory eicosanoid generation. (J Am Acad Dermatol 1998;38:539-47.)