Heat-shock proteins are induced in response to cellular stress. Although heat-shock proteins are known to function in repair and protective mechanisms, their relationship to critical neural processes, such as synaptic function, has received little attention. Here we investigate whether the major heat-shock protein Hsp70 localizes to the synapse following a physiologically relevant increase in temperature in the mammalian nervous system. Our results indicate that hyperthermia-induced Hsp70 is associated with pre- and postsynaptic elements, including the postsynaptic density. The positioning of Hsp70 at the synapse could facilitate the repair of stress-induced damage to synaptic proteins and also contribute to neuroprotective events at the synapse.