Subicular neurons receive direct afferent connections from the vast majority of CA1 pyramidal cells and send their axons to the various brain areas. Because of this strategic position, subicular cells can modulate output of the hippocampus and, thus, play a significant part in memory, spatial processing, and seizure amplification and propagation from the hippocampus. Despite its important role as a hippocampal interface with different brain regions, present knowledge of the subiculum and the plastic properties of the synapses on the subicular neurons is rather limited. By using IR-DIC videomicroscopy and whole-cell patch-clamp recordings in mouse hippocampal slices, I demonstrated that long-term potentiation (LTP) in CA1-subicular cell synapses can be readily induced by high-frequency stimulation (HFS) of the afferents, but not by pairing of low-frequency stimulation with depolarization of postsynaptic cells. This tetanus-induced LTP is input specific, insensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist 3-[(R)-2Carboxipiperazin-4-yl]-propyl-1-phosphonic acid (R-CPP), and reduces paired-pulse facilitation in potentiated synapses. Subsequent morphologic analysis of the recorded cells, which were filled either with Lucifer Yellow or Biocytin, revealed pyramidal-shaped neurons localized predominantly in the deep layer of the subiculum, close to the CA1 border. Axons of the majority of these neurons extended to the alveus and on toward the hippocampus, probably exiting it via the fornix. These data indicate that CA1-subicular cell synapses in mice exhibit LTP, which can be expressed presynaptically, and its induction does not require NMDA-receptor activation. The observed activity-dependent plasticity might play an important role in the integrative mechanisms of the subiculum and may influence transfer of information from the hippocampus to subcortical and cortical brain areas.