BACKGROUND: In several studies dietary fish oil has been found to have beneficial effect on psoriasis, but the results are contradictory and based mainly on open studies or studies of small numbers of patients. METHODS: In a four-month double-blind, multicenter trial, we randomly assigned 145 patients with moderate-to-severe psoriasis to receive in their diet either highly purified ethyl esters of n-3 fatty acids ("fish oil"; 6 g of oil per day, containing 5 g of eicosapentaenoic and docosahexaenoic acid) or an isoenergetic amount of corn oil containing mainly n-6 fatty acids. All the patients were advised to reduce their intake of saturated fatty acids. A 48-hour dietary recall was performed, and the fatty-acid pattern in the serum phospholipids was monitored in a subgroup of patients. RESULTS: In the fish-oil group, n-3 fatty acids were increased in serum phospholipids (P < 0.001), the ratio of arachidonic acid to eicosapentaenoic acid decreased (P < 0.001), and the level of n-6 fatty acids decreased (P < 0.001). In the corn-oil group, only docosahexaenoic acid increased significantly (P < 0.05). The ratio of polyunsaturated to saturated fatty acids increased in both groups. Plasma concentrations of triacylglycerol decreased from base line in the fish-oil group (P < 0.05). The score on the Psoriasis Area and Severity Index, as evaluated by the physicians, did not change significantly during the trial in either group. This was also true of a total subjective score reported by the patients, but a selected area of skin in the corn-oil group showed a significant reduction in the clinical signs (P < 0.05). Scaling was reduced from base line in both groups (P < 0.01). The fish-oil group had less cellular infiltration (P < 0.01), and the corn-oil group had improvement in desquamation and redness (P < 0.05). There was no significant difference in clinical manifestations between the groups. Among the patients in the fish-oil group, an increase in the concentration of n-3 fatty acids in serum phospholipids was not accompanied by clinical improvement, whereas in the corn-oil group there was a significant correlation between clinical improvement and an increase in eicosapentaenoic acid and total n-3 fatty acids. CONCLUSIONS: Dietary supplementation with very-long-chain n-3 fatty acids was no better than corn-oil supplementation in treating psoriasis. Clinical improvement was not correlated with an increase in the concentration of n-3 fatty acids in serum phospholipids among the patients in the fish-oil group, whereas there was a significant correlation between clinical improvement and an increase in eicosapentaenoic acid and total n-3 fatty acids in the corn-oil group.