In anemic patients on regular hemodialysis (HD), correction of anemia with recombinant human erythropoietin (rHuEpo) administered intravenously (iv) or subcutaneously (sc) was followed over a 2-month period. Monitoring serum Epo post-dose concentrations after the first iv rHuEpo injection and following another regular injection after 2 months of therapy with rHuEpo iv in 9 patients showed that the Epo elimination half-life was reduced from 7.48 h to 4.68 h. In the same patients the initially low percentage of erythroblasts and mature erythroid progenitors increased during 2 months of rHuEpo therapy. Because Epo molecules bound to Epo receptors are internalized in target cells we suggest that the expansion of the Epo responsive cell pool could explain the shorted Epo elimination time after 2 months of rHuEpo treatment. By monitoring serum Epo concentration following sc rHuEpo injection in 7 HD patients it was found that the modest increase in serum Epo levels (30-60 mU/ml) was sufficient to correct anemia.