Senescent organisms respond poorly to hypoxic stress. The transcription factor hypoxia-inducible factor 1 (HIF-1) plays a critical role in the coordinated genetic program that is induced in all tissues to adapt to hypoxic stress by binding to a specific DNA hypoxia-responsive recognition element (HRE). This study was designed to address whether aging is associated with an alteration in HIF-1 production and function. Young and old mice were exposed to hypoxia for various lengths of time. We found a severe impairment in the capacity of the old animals to form a HIF-1-HRE complex. This attenuation in the capacity to form HIF-1-HRE complexes in senescent tissues may explain the decreased ability of such tissues to respond to hypoxic stress.