Erythropoietin (EPO) is known to be a hematopoietic growth factor and a regulator of red blood cell production. Recently, EPO has also been reported to function as a tissue-protective cytokine and as an angiogenesis promoting factor. EPO is mainly regulated by hypoxia through the action of hypoxia inducible factors (HIF-1alpha and HIF-2alpha). The localization of the EPO protein and the HIF-2alpha protein were immunohistochemically analyzed in developing porcine embryos. Both proteins were localized in developing cartilage tissue. HIF-2alpha and EPO protein were expressed in the peripheral chondrocytes of cartilage anlagen, in the perichondrium and in the cell condensations that will eventually differentiate into cartilage tissue. The results of this study reveal that EPO might play a role as a survival factor or as a mitogen in developing cartilage tissue. Moreover, the presence of both proteins at the same locations supports the hypothesis that EPO expression is regulated by HIF-2alpha.