Erythropoietin (EPO) produced by the fetal liver and adult kidney is an essential stimulator of erythropoiesis. EPOproduction is regulated through hypoxic activation of gene transcription and possibly hypoxia-induced sta-bilization of its mRNA. In the liver of early embryos in which EPO production poorly responds to hypoxia, retinoic acid maybe an important stimulator. In this decade, newsites of EPOproduction have been found: cen-tral nervous system and reproductive organs. These tissues have a paracrine and/or autocrine systemof EPO, which is independent of the endocrine system (kidney/bone marrow) in adult erythropoiesis. In the central nervous system, astrocytes are the main producers of EPO, while EPOreceptor is expressed in neurons. EPO protects neurons from a various types of damage. The uterine EPOis likely involved in the estrogen-dependent angiogenesis of the endometrial layer. The possible functions of EPOin other tissues and tissue-characteristic regulation of EPOproduction are also discussed in this review.