Numerous lines of evidence suggest that some of the neurotoxicity associated with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid precursor protein (APP). Most research has focused on the amyloid beta peptide (Abeta). However, the possible role of other cleaved products of APP is less clear. We have previously shown that a recombinant carboxy-terminal 105 amino acid fragment (CT 105) of APP induced strong non-selective inward currents and also showed neurotoxicity in PC 12 cells and primary cortical neurons and blocked later phase of long term potentiation (LTP) in rat hippocampus in vivo. In this study, we investigated the effects of CT 105 on Na+-Ca2+ exchanger activity in SK-N-SH human neuroblastoma, in the presence of ouabain and monensin, which are considered to drive Na+-Ca2+ exchanger in the reverse mode. CT 105 inhibited the activity of this exchanger in SK-N-SH cells by approximately 50%.