THE aim of the present study was to determine whether amyloid β-peptide (Aβ) induces mitochondrial dysfunction. Mitochondrial function was reported to be affected following Aβ exposure, as demonstrated by depolarization of the mitochondrial membrane, decrease of oxygen consumption and by the inhibition of complexes I, III and IV of the mitochondrial respiratory chain. Aβ25-35 and Aβ1-40 peptides also inhibited MTT reduction in a dose-dependent manner in undifferentiated and differentiated PC12 cells. Several antioxidants prevented this inhibitory response, suggesting that oxidative stress is involved in Aβ-induced cytotoxicity. These data suggest that mitochondrial dysfunction contributes to amyloid β-protein cytotoxicity and may play a major role in the abnormalities of energy metabolism observed in Alzheimer's disease.