Hsp70 is induced by hypoxia in most mammalian cell types and contributes to their ability to survive hypoxic episodes, However, little is known about Hsp70 expression in the hypoxia-tolerant endothelial cells (ECs), We investigated the effect of hypoxia on Hsp70 in human microvascular endothelial HMEC-1 cells, Reduction of pO(2) to 2.5% of normal for 20 h stimulated lactate production and the activity of glycolytic enzymes, This metabolic adaptation to hypoxia was accompanied by a remarkable reduction of Hsp70 on the protein level and on the mRNA level, Approximately 12 h after the hypoxic period Hsp70 expression reached pre-hypoxia levels again. Since ECs are adapted to the low oxygen tension of the vasculature they are confronted with a supraphysiological oxygen level during in vitro culture. We suppose that the high Hsp70 under these conditions reflects a stress response which disappears at the more physiological reduced oxygen tension during hypoxia.