NADPH oxidases are thought to be the major source of pro-atherosclerotic vascular superoxide anion formation. Comparision of subunit expression and NADPH oxidase activity of human phagocytes and endothelial cells suggested that the expression of the subunit gp91-phox might determine endothelial NADPH oxidase activity. Oxidatively modified "low density"-lipoprotein (oxLDL) and angiotensin II (Ang II), both known to cause oxidative stress in the vessel wall, induced the expression of gp91-phox and NADPH oxidase activity in endothelial cells. Depending on the Ang II concentration, a bimodal regulation of the NADPH oxidase activity could be demonstrated that was exclusively related to the Ang II-dependent regulation of gp91-phox expression. This observation adds further prove to the postulated determinant role of gp91-phox expression. Furthermore, the expression of an endothelial oxLDL receptor LOX-1, the putative mediator of oxLDL-induced expression of gp91-phox, was shown to be induced by Ang II. Therefore, Ang II might further augment the oxLDL-induced gp91-phox expression. Chronical treatment with HMG-CoA reductase inhibitors and AT1 receptor blockers respectively reduced the expression of gp91-phox, as was demonstrated in biopsies of internal mammary arteries from patients with coronary heart disease. The expression of LOX-1 was reduced by chronical treatment with ACE inhibitors. These data confirm, that the regulatory mechanisms of gp91-phox and LOX-1 expression, as determined in vitro, may also be relevant in vivo. The results of the study were summarized in a pro-atherosclerotic Circulus vitiosus of endothelial radical formation.