Patients with chronic renal failure exhibit plasma fatty acid patterns indicative of essential fatty acid deficiency. The plasma fatty acid profile of 25 hemodialysis patients with a history of pruritus symptoms indicated lower 20:3n-9 (eicosatrienoic acid), 20:4n-6 (arachidonic acid), and 20:5n-3 (eicosapentaenoic acid) concentrations; a higher 18:1n-9 (oleic acid) concentration; and above-normal ranges of prostaglandin E2 (PGE2) compared with 22 subjects chosen from a normal population. No significant difference in 22:6n-3 (docosahexaenoic acid) was shown between the hemodialysis patients and the normal subjects. The dietary intake of 20:5n-3 was higher and that of 18:1n-9 lower in the patients compared with the normal population group. In this 8-wk double-blind study the hemodialysis patients were randomly assigned to receive daily supplements of 6 g ethyl ester of either fish oil, olive oil, or safflower oil. At the end of 8 wk of treatment the fish oil group (FO group) had a greater decrease in 18:1n-9 (P < 0.05), greater increases in 20:5n-3 and 22:6n-3 (P < 0.01), and trends toward a greater decrease in 20:4n-6, a greater increase in PGE2 concentrations, and greater improvement in pruritus scores (0.10 > P > 0.05) compared with the other two groups. The increases in 20:5n-3 and 22:6n-3 in the FO group indicate compliance with fish oil supplementation. Results indicate that hemodialysis patients have abnormal fatty acid profiles and increased PGE2 values. Fish oil intervention changes the fatty acid profile and may improve the symptoms of pruritus.