Some evidence suggests that aluminum is one of the risk factors in Alzheimer's disease (AD); however, there is no study on the relationship between the synaptic configuration changes and aluminum uptake. In the present study, 40 rats were fed with water solution aluminum for 3 months and the effects of aluminum on the Gray's type I synapses in hippocampus and frontal cortex of rats were quantitatively investigated by electron microscopy. The effects of aluminum on the ability to learn and memorize were tested by a Morris water maze. Length of synaptic active zone, width of synaptic cleft, curvature of synapse, and thickness of postsynaptic density (PSD) were measured in the interface of synapses by the IBM-PC microimage processing system. The flat synapse, positive and negative curvature synapses, as well as the perforated synapse were classified and counted according to the type of the interfacial structure of a synapse. The amounts of aluminum deposited in brain were measured with an atomic absorption spectrophotometer. Our results show that the time and the distance taken by the rats to find the water maze increased after the rats were fed aluminum for 3 months. As compared with control, the synapses in aluminum-induced rats exhibited the following significant changes: decreased thickness of PSD (P < 0.01), increased width of synaptic cleft (P < 0.05), increased numbers of flat synapse, decreased numbers of positive curvature synapse and perforated synapse, and significantly increased aluminum deposits in hippocampus and frontal cortex (P < 0.01). Our study indicates that aluminum can decrease the ability of rats to learn and memorize and induce their synaptic configuration changes. These changes may be related to synaptic efficacy and may be one of the mechanisms for AL to induce AD. Synapse 52:292–298, 2004. © 2004 Wiley-Liss, Inc.