Epoetin alfa and beta are the two forms of recombinant DNA-derived erythropoietin (rEPO), both synthesized in Chinese hamster ovary cells, which are used for the treatment of erythropoietin (EPO)-responsive anaemias.Several batches of each of these rEPOs were compared for differences in their EPO isoform compositions by isoelectric focusing (IEF) and in a range of lectin-binding assays,and for differences in their EP0 activities by in-vivo and in-vitro mouse bioassays and by immunoassay.Epoetin beta was found to differ from epoetin aria in containing: (a)a greater proportion of more basic isoforms,(b) a greater proportion of EPO binding to Frythrina cristagalli agglutinin (which binds N-glycans with nonsialylated outer Galβ1-4GIcNAc moieties), and ? isoforms with higher in-vivo:in-vitro bioactivity ratios.Epoetin beta also contained slightly more than epoetin alfa of EPO binding to Lycopersicon esculentum agglutinin (which binds N-glycans containing repeating Galβl-4GlcNAc sequences), to the leucoagglutinin of Phaseolus vulgaris (which binds tetraantennary and 2,6-branched triantennary N-glycans) and to Agaricus bisporus agglutinin (which binds Galβl-3GalNAc containing O-glycans).No differences were found between the two rEPOs in their binding to a further five lectins.The differences between the isoform composition of epoetin alfa and beta, and the smaller inter-batch differences appear to be due to differences in glycosylation.The higher murine in-vivo:in-vitro bioactivity ratio of epoetin beta compared to epoetin alfa could not be explained in terms of differences in their degrees of sialylation, but was consistent with differences in their pharmacokinetics and pharmacodynamics observed in human subjects.There have been no reports that epoetin alfa differs from epoetin beta in its clinical efficacy, but the differences between epoetin alfa and beta in some analytical systems suggest that there might be a need for separate international standards for these two types of rEPO.