Hypoxia-inducible factor 1 (HIF-1) is a heterodimer composed of two subunits, HIF-1α and HIF-1β (ARNT), which are both basic-helix-loop-helix-PAS proteins. HIF-1α is most similar to the Drosophila protein Sim, while HIF-1β is a series of ARNT gene products. Both subunits are regulated by cellular oxygen tension and are necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. HIF-1α and HIF-1β RNA and protein levels are induced in cells exposed to low oxygen tension (1% O2) and decay rapidly upon return to normal oxygen levels. The results suggest that HIF-1 plays a general role in activating homeostatic responses to hypoxia, such as erythropoiesis, neovascularization, and glycolysis. The molecular mechanisms underlying HIF-1 activity include both transcriptional and posttranscriptional regulation, with potential ligand binding also being considered. The findings provide insights into the molecular mechanisms by which HIF-1 regulates mammalian oxygen homeostasis.Hypoxia-inducible factor 1 (HIF-1) is a heterodimer composed of two subunits, HIF-1α and HIF-1β (ARNT), which are both basic-helix-loop-helix-PAS proteins. HIF-1α is most similar to the Drosophila protein Sim, while HIF-1β is a series of ARNT gene products. Both subunits are regulated by cellular oxygen tension and are necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. HIF-1α and HIF-1β RNA and protein levels are induced in cells exposed to low oxygen tension (1% O2) and decay rapidly upon return to normal oxygen levels. The results suggest that HIF-1 plays a general role in activating homeostatic responses to hypoxia, such as erythropoiesis, neovascularization, and glycolysis. The molecular mechanisms underlying HIF-1 activity include both transcriptional and posttranscriptional regulation, with potential ligand binding also being considered. The findings provide insights into the molecular mechanisms by which HIF-1 regulates mammalian oxygen homeostasis.