These studies were to evaluate the effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors by the in vivo plasma clot diffusion chamber and the in vitro plasma clot culture methods. Changes in the plasma erythropoietin levels in the reticulocyte concentration and hematocrits of irradiated and nonirradiated Long-Evans rats exposed to hypoxia were also determined. While erythropoietin plasma concentrations appeared to affect BFU-E and CFU-E growth, results suggest erythropoietin may not be the sole regulator of red cell production and that inhibitors of chalone-like mechanisms may be involved. Measurements made on granulocyte precursors treated with colony stimulating factor (CSF) containing L-cell-conditioned medium revealed granulocytic colonies and burst-like formations similar to those seen for erythrocytic growth. There is strong evidence suggesting that CSF is a regulator of granulopoiesis; however, it is not the sole regulator and it appears that inhibitors may play an in vivo role. Growth of colonies with cell numbers not a power of 2 implies either asymmetric mitosis due to loss of genetic information required for continuing division, or differences in concentrations of, or ability to recognize, inhibitory factors. These possibilities are examined in the light of results from in vivo and in vitro culture techniques.