Myeloid cells recruited to sites of bacterial inflammation are exposed to low oxygen tension, hypoxia, and high concentrations of inflammatory cytokines which will both significantly affect myeloid cell function. Therefore, we analyzed the direct consequences of acute and severe hypoxia on monocytic adhesion to the endothelium in coculture experiments. Marked upregulation of monocytic ICAM-1 but not CD18 was responsible for an almost 50-fold increase in adhesion of the monocytic cells THP-1 to human and rat endothelial cells. ICAM-1 expression was rapidly induced after the onset of severe hypoxia but decreased again after 4 hours. Knock-down of ICAM-1 by siRNA in endothelial as well as in monocytic cells abolished the adhesion, indicating that ICAM-1 expression on both cell types was indispensable for hypoxia induced adhesion of monocytes to the endothelium. SiRNA mediated knock-down of HIF-1a and HIF-2a revealed that hypoxic upregulation of ICAM-1 resulted from hypoxic NF-kB induction but not from activation of HIF-1. Within the leukocyte adhesion cascade our results provide evidence for prolyl hydroxylase dependent but HIF independent activation of hypoxia-induced monocyte-endothelial adhesion and assign a new function to monocytic ICAM-1 under acute hypoxic conditions.