Chronically anemic baboons on a continuous hydroxyurea regimen were treated with pulsed doses of recombinant human erythropoietin (rHuEpo) to test whether the combination of these two compounds, which individually induce F-cell production, can enhance further F-cell output. A low-F-cell-responding animal under chronic hydroxyurea treatment was given three separate pulses of Epo and responded with F-reticulocyte increments that were similar to the sum increments caused by either hydroxyurea alone or rHuEpo alone. The same results were obtained in a high-F-responding animal similarly treated. These findings suggest that rHuEpo and hydroxyurea can increase F cell numbers in an additive fashion. It is speculated that both compounds act through perturbation of erythroid differentiation kinetics.