Chlamydiae are a family of obligate intracellular bacterial pathogens that must replicate within cytoplasmic vacuoles of eukaryotic cells. To complete their intracellular replication they have to protect the infected cells from host immune recognition and effector mechanisms. Besides some other strategies for evading host defense, Chlamydiae secrete the "chlamydial proteasomal like activity factor" (CPAF) into the cytoplasma of infected cells. Hypoxia inducible factor-1 (HIF-1) is a a/bdimeric transcription factor mediating the cellular responses to hypoxia. In the presence of oxygen the a-subunit is immediately hydroxylated at specific prolyl- and aparagyl-residues, thereby becoming tagged for proteasomal degradation. We show that HIF-1a is degraded in Chlamdia-infected cells irrespectible of the oxgen concentration and that this degradation is CPAF-dependent, implying an important role of HIF-1 in immune defense.