Minor components of virgin olive oil (VOO) may play a key role in the beneficial effects of VOO on atherosclerosis. In the present study we evaluated the influence of the unsaponifiable fraction of VOO on the production of eicosanoids and nitric oxide (NO) by endothelial cells (HUVECs). Triglyceride-rich lipoprotein (TRLs) were isolated from human serum after the intake of meals enriched in 3 high-oleic acid oils, i.e., high-oleic sunflower (HOSO), VOO, or enriched-virgin olive (EVO) oils, the last-mentioned containing 2.4% of unsaponifiable matter. HOSO induced a greater accumulation of triglycerides (TGs) in the postprandial serum than VOO or EVO, as measured by calculating the area under the curve. The incubation with TRLs increased NO release by endothelial cells compared with untreated control cells, but the effects of the various TRLs did not differ. EVO-derived TRLs reduced the production of prostaglandin E(2) (PGE(2)) and thromboxane B(2) (TxB(2)) (the stable metabolite of TxA(2)) compared with VOO- or HOSO-derived TRLs. The release of PGI(2) (as 6-keto PGF(1alpha)) was similarly diminished by all TRLs compared with the control. In conclusion, the unsaponifiable fraction of VOO does not affect postprandial triglyceridemia, but it has favorable effects on endothelial function, mainly by reducing proinflammatory and vasoconstrictor eicosanoid synthesis (PGE(2) and TxB(2)).