Dendritic cells (DCs) are an important link between innate and adaptive immunity. They are activated in inflamed tissues, where oxygen tension is usually low. In monocytes, hypoxia as well as inflammatory stimuli were shown to induce the regulatory a-subunit of the HIF (hypoxia inducible factor)-1 complex. To investigate whether this transcriptional complex also plays a pivotal role in the function of DCs we compared the effects of exogenous inflammatory stimuli and hypoxia on HIF-1a in bone marrow derived DCs from wildtype and myeloid specific HIF-1a knockout mice. We were able to show that hypoxia and inflammatory mediators such as LPS (lipopoly-saccharides) and POLY (I:C) (dsRNA) resulted in the accumulation of the HIF-1a protein. Likewise, HIF-1a mRNA was induced. Furthermore we studied the importance of functional HIF-1a protein for the expression of HIF-1 target genes. VEGF (vascular endothelial growth factor), GLUT-1 (glucose transporter-1) and PHD2 (prolyl hydroxylase 2) were identified as HIF-1 target genes induced in DCs. The potential to upregulate cytokines involved in viral infections critically influences DC function. Therefore we examined the correlation between the activity of HIF-1 and the induction of IFN (interferon)-a and -b. Altogether we can conclude that HIF-1a seems to play a crucial role for dendritic cell activation and functionality by coordinating the expression of several hypoxia-inducible genes important for DC function.