Receptor of advanced glycation end products (RAGE) was identified as one of the receptors for amyloid beta peptide (Abeta). There is evidence for controversial functions of RAGE such as a mediator of cell death or differentiation. In this report, we demonstrate that RAGE mediates Abeta toxicity. Transient transfection of RAGE already induced cell death. For further analysis, stable clones of hemagglutinin (HA)-tagged RAGE were selected. Analysis of cellular localization of HA-tagged RAGE protein revealed, in addition to the expected cell surface expression, a novel intracellular localization. Stable RAGE-expressing cells were hypersensitive to nanomolar amounts of Abeta. Only cells expressing RAGE at the cell surface showed hypersensitivity to Abeta.