Although the neurotoxicity of beta-amyloid peptide is well established, the cellular functions of amyloid precursor protein (APP) remain unclear. Using an adenoviral vector, we introduced cDNA encoding human APP holoprotein into rat hippocampal neurones in culture. Neurones expressing the membrane-bound form of APP showed greater responsiveness to applied glutamate than non-expressing control neurones, as revealed by Ca2+ fluorometry. This increased responsiveness was not the result of secreted APP, as confirmed by observations of closely spaced APP-expressing and non-expressing cells in the same culture dish. These data suggest that one function of APP may be the regulation of glutamate receptors in neurones.