The effects of Al3+ on Na+ and K+ channel activities in rat and rabbit hippocampal neurons have been examined. Al3+ mediated a pronounced voltage-dependent inhibition of single Na+ channel activities in inside-out patches excised from neuronal membranes. The reduction in channel activity was more substantial under defined conditions, particularly when changing the holding potential from -120 to -80 mV. This voltage-dependent block indicates that Al3+ can mainly inhibit the excitation of neurons with less negative resting potentials. The observed effect may be related to the pathogenetic mechanism of the specific action of Al3+ on defined types of neurons affected in neurodegenerative disorders such as Alzheimer's disease.