The aim of this research is to find out what factors determine choice of hemoglobin (Hb) types in red blood cells (RBCs) as they differentiate from pluripotent hemopoietic stem cells (PHSCs). Such knowledge would be of value in designing methods to potentiate fetal-type Hb in humans, to alleviate the effects of certain diseases such as Beta-thalassemias. All vertebrates undergo changes in the type of Hbs in their RBCs during ontogeny. The different Hb types have different structural and functional properties as a result of their being composed of different globin chains which are, in turn, the products of different genes. I have proposed that the type of Hb formed within RBCs is a choice influenced by the microenvironment (micro-milieu) surrounding the differentiating RBCs, within the erythropoietic organs. The expression of different Hb types in different RBC populations during ontogeny is hypothesized to result from changes within the microenvironments in which RBCs differentiate. Erythropoietic organ cultures, density-gradient separation of cell types, and hemopoietic cell transplants are among the approaches being used. The animal model being investigated is the switch from larval to adult Hbs during amphibian metamorphosis in two species, Rana catesbeiana and Xenopus laevis.