Aims: Amyloid peptides are formed during inflammation and modify the function of immune cells. The present study explored the effect of amyloid b-peptide (Ab_1-42) and islet amyloid polypeptide (IAPP) on mouse bone marrow derived dendritic cells (DCs). Methods: DCs were treated with Ab_1-42 (10-5000 nM, 24 h) or IAPP (0,05-10M, 24 h). Ceramide formation was determined with anti-ceramide antibodies in FACS, caspase activity utilizing FITC conjugated anti-active caspase 8 or caspase 3 antibodies in FACS and by western blotting, DNA fragmentation by determining the percentage of cells in the sub-G1 phase and cell membrane scrambling by annexin V binding in FACS analysis. TNF secretion was assessed in lypopolysaccharide (LPS)-stimulated amyloid peptide-treated DCs. Results: Within 24 h amyloid peptides triggered ceramide formation, caspase 8 and caspase 3 activation, DNA fragmentation and annexin V binding in DCs obtained from wild type mice, effects blunted in DCs from sphingomyelinase deficient (asm^-/-) mice and in wild type DCs treated with sphingomyelinase inhibitor amitriptyline. Moreover, ceramide formation was also reduced in wild type DCs in which acid sphingomyelinase (Asm) was silenced with Asm-targeted siRNA. Amyloid peptide treatment was further followed by a decline of TNFa formation in wild type DCs. Conclusion: Amyloid peptides induce DC apoptosis presumably through activation of Asm resulting in production of ceramide.