In the hippocampal formation many neuromodulators are possibly implied in the synaptic plasticity such as the long-term potentiation (LTP) induced by high-frequency stimulation (HFS) of afferent fibers. We investigated the involvement of locally synthesized neural 17β-estradiol (nE 2) in the induction of HFS-LTP in hippocampal slices from male rats by stimulating the Schaffer collateral fibers and recording the evoked field excitatory postsynaptic potential (fEPSP) in the CA1 region. We demonstrated that either the blockade of nE 2 synthesis by the aromatase inhibitor letrozole, or the antagonism of E 2 receptors (ERs) by ICI 182,780 did not prevent the induction of HFS-LTP, but reduced its amplitude by ~60%, without influencing its maintenance. Moreover, letrozole and ICI 182,780 did not affect the first short-term post-tetanic component of LTP and the paired-pulse facilitation (PPF). These findings demonstrate that nE 2 plays an important role in the induction phase of HFS-dependent LTP. Since the basal responses were not affected by the blocking agents, we suggest that the synthesis of nE 2 is induced or enhanced by HFS through aromatase activation. In this context, the local production of nE 2 seems to be a very effective mechanism to modulate the amplitude of LTP. © 2011 IBRO.