The regulation of erythropoiesis was studied in patients with polycythemia vera and chronic granulocytic leukemia (CGL). An in vitro culture system was employed to determine the response of bone marrow cells to erythropoietin. In normal subjects, iron incorporation into heme (during the 18th to 22nd hr of culture) was increased by 35% (mean) in erythropoietin-treated cultures as compared to control cultures. Erythropoietin was ineffective in stimulating iron incorporation into heme in five patients with polycythemia vera. The marrow response to erythropoietin in vitro was within the normal range in three patients with CGL (37% stimulation). Thus, the role of erythropoietin in the control of erythropoiesis in myeloproliferative syndromes appears variable.