Eicosapentaenoic acid (EPA) is one of the major components of fish oil, which was reported to have antiatherogenic, anti-inflammatory and immune suppressive effects. In the present study, highly purified EPA was administered to patients with lupus nephritis and the effects of EPA on urinary 8-isoprostane, a reliable marker of oxidative stress, were investigated in these patients. Six outpatients (1 man and 5 women), with lupus nephritis diagnosed by renal biopsy, were entered in the study. We administered 1800 mg EPA ethyl-ester (purity > 95%) daily and examined the urinary 8-isoprostane levels and plasma fatty acid composition before and 3 months after EPA treatment. The urinary 8-isoprostane levels were significantly decreased after the treatment compared with those before the treatment (from 530 +/- 113 pg/mg x Cr to 235 +/- 49 pg/mg x Cr, p = 0.02). The EPA levels in the plasma phospholipid (PL) fraction were significantly increased after the treatment (from 3.30 +/- 0.64 mol% to 8.01 +/- 0.47 mol%, p < 0.001). Arachidonic acid (AA) levels in the plasma PL fraction were significantly decreased after the treatment (from 9.47 +/- 0.28 mol% to 7.33 +/- 0.43 mol%, p < 0.001). The ratios of EPA to AA were significantly increased after the treatment (from 0.35 +/- 0.07 to 1.14 +/- 0.16, p < 0.001). Thus, this preliminary study indicated that EPA might exert beneficial effects on lupus nephritis by decreasing the oxidative stress.