Rats were rendered anaemic by a single bleeding or by a single injection of phenylhydrazine. At various times after the onset of anaemia they were nephrectomized and challenged with a 6 h exposure to hypoxia. The erythropoietin titre observed at the end of this hypoxic period was corrected for renal erythropoietin induced by the anaemia alone, and the resulting extrarenal component was compared to total erythropoietin production of nephric rats in response to anaemia plus 6 h hypoxia. Extrarenal erythropoietin production was found to increase from 10.3% in normal rats to 12.5% in moderately anaemic rats to 15.1% in rats with severe bleeding anaemia. In phenylhydrazine-treated rats this extrarenal component was found to be 18.3% possibly due to stimulation of extrarenal erythropoietin by haemolysed red cells. Chronic phenylhydrazine administration resulted in splenomegaly and Kupffer cell hyperactivity but not in any further stimulation of extrarenal erythropoietin production.

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Summary Neonatal erythroid cells in the bovine respond to erythropoietin in vitro with a pari passu increase in the synthesis of both foetal and adult haemoglobins. With marked stimulation the effect upon the latter predominates. The conditions of cell culture, however, promote the formation of a protein with chromatographic characteristics of foetal gamma‐globin subunits, quite independently of the presence of erythropoietin or of haem synthesis. The results suggest that erythropoietin might be assigned a significant although indirect role in the gradual switchover of haemoglobin types during development.

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