The dramatic increase in knowledge during the last half century about the hormone erythropoietin is reviewed. The description of these events has been separated into two parts. The first part describes how the rapid changes in response to tissue oxygenation in the kidneys changes the rate of erythropoietin production. The second part describes how changes in erythropoietin concentrations act on erythroid progenitor cells, resulting in prompt changes in rates of erythrocyte production. Together these two aspects of erythropoietin biology provide an explanation for the tight physiological regulation of the numbers of circulating erythrocytes and, in a more general manner, provide a model for the control of the numbers of other specific blood cells by their respective hematopoietic growth factors.