The present study was performed to investigate the effects of dietary fish oil supplements on renal function and renal prostaglandin (PG) E metabolism. The usual "western" diet of 10 healthy volunteers (six female and 4 male) aged between 21 and 35 years was supplemented with 6 g/day of n-3 polyunsaturated fatty acids [3.6 g of eicosapentaenoic acid (EPA) and 2.4 g of docosahexaenoic acid (DHA)] for six weeks. Supine arterial blood pressure (BP) and heart rate (HR), renal hemodynamics, renal excretory function and urinary excretion of PGE2 and PGE3 were determined before and at the end of the fish oil supplementation period. No changes could be observed in BP and HR while renal plasma flow (RPF), determined as the clearance of PAH, significantly increased from 559 ± 44 to 738 ± 47 ml/min (P < 0.001) with the fish oil supplements. This was associated with a decrease in renal vascular resistance from (8.11 ± 0.54) · 10-2 to (6.37 ± 0.38) · 10-2 mm Hg · min · ml-1 (P < 0.01). Glomerular filtration rate (GFR), determined as the clearance of inulin, increased from 97 ± 3 to 107 ± 3 ml/min (P < 0.01), resulting in a decrease in filtration fraction from an average of 0.19 ± 0.01 to 0.15 ± 0.01 (P < 0.01). This was paralleled by an increase in urine volume (V̇) (13.8 ± 0.9 vs. 12.2 ± 1.0 ml/min; P < 0.05), urinary excretion of inorganic phosphate (UPhosV; 20.6 ± 2.0 vs. 16.9 ± 2.0 μmol/min; P < 0.05) and CH2O (9.6 ± 0.6 vs. 8.5 ± 0.7 ml/min) in the presence of unchanged UNaV, UKV, UClV, COsm and CH2O/GFR determined during maximal water diuresis and hypotonie (0.45%) saline infusion. Urinary excretion of PGE2 determined in the six female participants decreased with the fish oil supplements (168.0 ± 13.0 vs. 125.3 ± 11.8 ng/24 hr; P < 0.01), while urinary excretion of PGE3 averaged 6.9 ± 0.8 ng/24 hr during control and increased to 23.4 ± 3.2 ng/24 hr (P < 0.01) with the n-3 fatty acid supplements. Our study demonstrates that supplementation of a regular "western" diet with EPA and DHA in the here chosen doses over six weeks markedly affects renal hemodynamics, with increases in RPF and GFR. In spite of an increased filtered load, unchanged electrolyte excretion implies increased tubular reabsorption which may, at least in part, be located in the diluting segments of the nephron. These renal hemodynamic and tubular functional changes are associated with quantitative and qualitative alterations in renal prostanoid metabolism. However, the precise interrelationship between the alterations in renal eicosanoid metabolism and the changes observed in renal hemodynamics and renal excretory function remains to be established.