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The first part of this study describes the hematologic and physiologic changes observed in sheep homozygous for the hemoglobin A during severe blood loss anemia. It was found possible thus experimentally to replace Hb A entirely with a new hemoglobin type, Hb C. The following additional observations were made: (1) Hb C could not be distinguished from Hb A by submitting the appropriate red blood cells to an "acid elution" technic. These two hemoglobin types were found to be more resistant to this treatment than a second adult hemoglobin type, Hb B, while the fetal hemoglobin of the new-born lamb was found to be highly resistant. In sheep heterozygous for Hb A and Hb B, both hemoglobin types were equally distributed among all red blood cells. (2) During stages of severe blood loss relatively small quantities of acid resistant red blood cells of larger size were demonstrable in homozygous Hb A sheep; these cells were considered to be reticulocytes. Additional observations regarding variations in red cell parameters are also presented. (3) The oxygen affinities and the Bohr effects of blood samples and red cell hemolysates containing over 90 per cent Hb C are presented and compared with those of samples containing only Hb A, Hb B or the hemoglobin of the newborn lamb. Attempts to produce Hb C in sheep homozygous for Hb A by means other than phlebotomy are described in the second part of this report. Small amounts of Hb C were demonstrable in a sheep homozygous for Hb A after repeated injections of a urinary extract of human origin with high erythropoietic activity. Administration of cobalt and of thyroxin did not result in the formation of significant amounts of Hb C.

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