The effects of Alzheimer's disease-related beta-amyloid (Abeta) peptides on the N-methyl-D-aspartate (NMDA)-evoked cell firing rate were studied in hippocampal CA1 neurons of the rat. Extracellular single-unit recordings were combined with iontophoretic applications that allowed quantitative analyses of the interactions between Abeta peptides and NMDA receptor-mediated events in vivo. The NMDA responses were significantly increased both by the full length Abeta1-42 and by its model fragment Abeta25-35. Enhancements of the NMDA responses by the Abeta peptides lasted about 15 min and were irreversible. The effects of Abeta25-35 were prevented by the pentapeptide Lys-Leu-Val-Gly-Phe-amide (KLVGF) and were not evoked when its reversed sequence (Abeta35-25) was applied.