Recent findings suggest that recombinant human erythropoietin (rhEpo) may have an immunomodulating action. We have studied the in vitro and in vivo effects of rhEpo on immune functions in man. Low pharmacological concentrations of the hormone inhibit T-cell activation and proliferation, while higher ones are without that effect. The same Epo concentrations inhibit mitogen- and alloantigen-driven B-cell differentiation and immunoglobulin synthesis and, to a lesser extent, B-cell proliferation. In vivo treatment with rhEpo causes an initial inhibition of T- and B-cell proliferation, but with prolonged administration improved responsiveness is observed. Our data support the notion that rhEpo can regulate immune functions, a fact of potential clinical application.