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Abstract: Aims: To apply modern mass spectrometry based technology to identify possible CSF peptide markers of glioblastoma multiforme (GBM). Methods: Mass spectrometry based peptidomics® technology enables a systematic and comprehensive screening of cerebrospinal fluid (CSF) with regard to its peptide composition. Differential Peptide Display® (DPD) allows the identification of single marker peptides for a target disease. Using both, we analyzed CSF samples of 11 patients harbouring a glioblastoma multiforme in comparison to 13 normal controls. Results: Four CSF peptides which significantly distinguished GBM from controls in all applied statistic tests could be identified out of more than 2000 detected CSF peptides. They were specific C-terminal fragments of alpha-1-antichymotrypsin, osteopontin, and transthyretin as well as a N-terminal residue of albumin. All molecules are constituents of normal CSF, but none has previously been reported to be significantly elevated in CSF of GBM patients. Conclusion: The study showed that peptidomics technology is able to identify possible biomarkers of neoplastic CNS disease. It remains to be determined if the identified elevated CSF peptides are specific for GBM. With regard to GBM, however, the more important role of CSF peptide biomarkers than aiding initial diagnosis might be early recognition of disease recurrence or monitoring of efficacy of adjuvant therapy protocols. [Copyright &y& Elsevier]