Abstract Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [Epa]and 12% C22:6 n-3 docosahexanoic acid [Dha]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsAtreated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 ± 0.02% to 4.6 ± 0.5%, P < .0001) and DHA (from 1.8 ± 0.2% to 3.9 ± 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 ± 2% to 28.4 ± 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% ( P = .012), the glomerular filtration rate increased by 33% ( P = .057), the renal blood flow increased by 17% ( P = .024), and the calculated total renal vascular resistances decreased by 20% ( P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during l-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group. The urine excretion of Tx B 2 decreased from 707 ± 192 to 276 ± 76 pg/hr ( P = .013) in fish oil group, whereas it increased from 428 ± 195 to 870 ± 310 pg/hr ( P = .016) in corn oil group. In conclusion, 2 months of diet supplementation with fish oil in stable CsA-treated liver transplant recipients was associated with significant improvement of renal hemodynamics and with significant reduction of the renal production of TxB 2.