Inflammatory bowel diseases are widespread and severe, with Crohn's disease and ulcerative colitis representing the most prevalent types. It is increasingly recognized that inflammatory processes are always associated with low oxygen tension (hypoxia). Tissue hypoxia requires adaptation of the cells which is mainly controlled by transcription factors designated hypoxia-inducible factors (HIFs), composed of oxygen-regulated a-subunits and a constitutive HIF-1b. Herein, we analyzed how the activation of HIF-1a and HIF-2a subunits in myeloid cells (neutrophil granulocytes, monocytes/macrophages and dendritic cells) influences the progression of an acute colitis. To this aim, mice with a conditional knockout of HIF-1a or HIF-2a either in myeloid cells or in dendritic cells were treated with dextran sodium sulfate to induce experimental colitis. The severity of disease was determined by general outcome, weight loss, and measurement of colon weight and length. We determined the number and distribution of mononuclear cells in colon sections from control and knockout mice using immunohistologic analysis. Expression of hypoxia-inducible genes in the inflamed colon was studied at the mRNA level. First results show that mice lacking HIF-1a in myeloid cells started to lose weight at an earlier time point than controls. Colon samples of these animals showed higher amounts of HIF-2a positive leukocytes and increased expression of inflammatory genes. We conclude that loss of hypoxia-inducible factors in immune cells may lead to augmented inflammation in an experimental model of acute colitis.