Plasma-derived high density lipoproteins (HDL) were found to inhibit cytokine-induced expression of endothelial cell adhesion molecules. Here we used apolipoprotein-specific reconstituted HDL (rHDL) made with phosphatidylcholine (PC) and three different apolipoproteins to identify the HDL components involved in this effect. rHDL containing apolipoprotein A-I (apoA-I), the disulfide-linked form of the apoA-IMilano variant, or apoA-II, were all effective in inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 in TNF alpha- or LPS-stimulated HUVEC. The inhibition was concentration dependent in the range of 0.1-1.0 mg/ml (protein). PC liposomes slightly depressed TNF alpha-induced VCAM-1 expression (16% vs 43-50% for the various rHDL), whereas the lipid-free apolipoproteins had no effect. The protein component of HDL is involved in the inhibition of VCAM-1 expression in HUVEC through a rather unspecific mechanism, as three apolipoproteins with remarkably different primary structure display very similar activity.