Monocyte adhesion to human aortic endothelial cells (ECs) is one of the early events in the development of atherogenesis. ECs were used to investigate the role of vitamin E in human monocyte adhesion to ECs in vitro. ECs incubated with 40 to 193 mg/dL of low-density lipoprotein cholesterol (LDL) for 22 hours exhibited increasing dose-dependent adherence for untreated, isolated human monocytes (P < .05). ECs exposed to the highest dose of LDL (193 mg/dL) but pretreated with 19 mumol/L alpha-tocopherol for 24 hours showed a trend to lower adherence for monocytes compared with non-treated ECs (4.4 +/- 1.2% versus 7.6 +/- 1.9%; P = .09). This effect of vitamin E became more significant (P < .05) when ECs were exposed to a lower level of LDL (40 mg/dL) or were pretreated with a higher level of alpha-tocopherol (42 mumol/L) and then exposed to 80 mg/dL LDL. Presupplementation of ECs with 15, 19, and 37 mumol/L alpha-tocopherol significantly (P < .05) reduced monocyte adhesion by 6 +/- 1%, 37 +/- 6%, and 69 +/- 17%, respectively. Levels of soluble intercellular adhesion molecule-1 (sICAM-1), one of the adhesion molecules for monocytes, increased after incubation of ECs with LDL 80 mg/dL (4.7 +/- 0.7 versus 6.4 +/- 1.2 ng/mL, respectively; P < .05). Treatment of ECs with alpha-tocopherol (42 mumol/L) significantly reduced induction of sICAM-1 by LDL to 2.2 +/- 2.3 ng/mL. After exposure to LDL, prostaglandin I2 production by ECs was diminished, whereas presupplementation of ECs with alpha-tocopherol partially reversed the LDL effect. Production of interleukin-1 beta was not detectable when ECs were treated with alpha-tocopherol, LDL, or alpha-tocopherol followed by LDL. Our findings indicate that vitamin E has an inhibitory effect on LDL-induced production of adhesion molecules and adhesion of monocytes to ECs via its antioxidant function and/or its direct regulatory effect on sICAM-1 expression.