The role of erythropoietin (Ep) in the regulation of erythroid committed precursor (ECP) population size was studied. Experiments were performed on polycythemic CBA mice treated with cyclophosphamide (Cy) on the 5th day after hypertransfusion. In these animals no erythropoietin-responsive cell (ERC) regeneration could be detected up to day 10 after Cy. The results obtained demonstrate that regeneration of ERC could be prompted if the test dose of Ep(2 U) was preceded by daily injections of 1 U Ep. Furthermore, one injection of 5 U Ep given 72 h before Ep test dose, at the time when pre-ERC were nearly completely recovered, was sufficient to stimulate ERC regeneration. At the same time hydroxyurea suicide was not changed in polycythemic mice treated with Cy and daily Ep injections as compared to control animals. The results indicate that Ep does not stimulate only the multiplication of ERC bu also progression of pre-ERC to ERC. In this way the population size of regenerating ECP is Ep dependent.