The present study examined the effect of purified eicosapentanoic acid (EPA) on intimal thickening of an autogenous vein graft. In addition, experiments were performed to determine whether EPA supplementation would alter the endothelium-dependent responses of the reversed vein graft. Segments of femoral veins were grafted into the femoral arteries of dogs. Six dogs received regular chow (control group) and six other dogs regular chow with 1500 mg/day 90.0% pure EPA (EPA group). At 6 weeks after surgery, the vein grafts were removed from the dogs, cut into rings, and suspended in organ chambers for isometric tension recording. In some rings, the endothelial cells were removed. When the rings taken from the control group were contracted with norepinephrine, adenosine diphosphate (ADP) and A23187 caused endothelium-dependent relaxations. In the EPA group, the endothelium-dependent responses to ADP were significantly augmented, while A23187 caused comparable endothelium-dependent relaxations. Direct relaxation in response to sodium nitroprusside was comparable between the two groups. Intimal thickening of the grafts in the control group (29.0 +/- 1.8 microns) was significantly (P < 0.05) greater than in the EPA group (12.5 +/- 1.8 microns). These results suggest that EPA enhances the release of endothelium-derived relaxing factor in autogenous vein grafts. This may be one of the effects of EPA in reducing the intimal thickening of autogenous vein grafts.