A recombinant fusion protein comprising a human erythropoietin peptide portion linked to an immunoglobulin peptide portion is described. The fusion protein has a prolonged half-life in vivo compared to naturally occurring or recombinant native human erythropoietin. In one embodiment, the protein has a half-life in vivo at least three-fold higher than native human erythropoietin. The fusion protein exhibits enhanced erythropoietic bioactivity compared to native human erythropoietin. In one embodiment, the fusion protein comprises the complete peptide sequence of a human erythropoietin (EPO) molecule and the peptide sequence of an Fc fragment of human IgG1, which Fc fragment includes the hinge region, CH2 and CH3 domains. The EPO molecule may be linked directly to the Fc fragment to avoid extraneous peptide linkers and lessen risk of an immunogenic response when administered. In one embodiment the hinge region is a human Fc fragment variant having a non-cysteine residue at amino acid 6.