Erythropoietin (Epo) is a hematopoietic growth factor that acts via activation of its cognate receptor (EpoR). Administration of Epo is well-established in the clinical treatment of the anemia associate with chronic renal failure, AIDS, cancer and chemo-therapy. Recently it has been postulated that the administration of Epo may also stimulate tumour cell proliferation and metasta-sis and that EpoR expression may be induced by hypoxia. We therefore investigated effects of Epo and hypoxia on cell-proliferation, EpoR expression, and activation of intracellular signalling cascades in various human tumour cell lines by RT-PCR, immunofluorescence and Western Blotting. We detected low levels of EpoR mRNA in all cell types, which was not changed by hypoxia or Epo treatment. Visualisation of endogenous EpoR using commercially available anti-EpoR antibodies generated a highly variable staining of the cell membrane and the cytoplasm. Protein-sequencing revealed that the antibodies interacted with non-EpoR proteins, e.g. HSP90. Furthermore, Epo treatment alone or combined with hypoxia did not modulate cell proliferation. In contrast, MAP-kinases were activated by Epo in all cells tested, however distinctly weaker than in an Epo dependent cell line (UT7/Epo). Thus we conclude that the detection of EpoR protein using the currently available antibodies does not predict adverse effects of EPO