In brain slices of normal Wistar and Long-Evans rats, brief high frequency stimulation of the fimbria fibers induced long-term potentiation (LTP) in excitatory transmission between these fimbria fibers and neurons of the lateral septum (LS). Slices prepared from diabetes insipidus (DI) Brattleboro rats, that contained no vasopressin (VP), consistently failed to maintain LTP in this excitatory transmission. Exogenous VP, administered to slices from DI Brattleboro rats shortly prior to the experiment or released from a subcutaneous depot in DI Brattleboro rats for several days prior to decapitation, corrected this failure. The maintenance of LTP in the LS in slices from Wistar and Long-Evans rats was prevented by D(CH2)5-Tyr(Me)-arginine VP, an antagonist for the V1 type of VP receptors. These results indicate an important role of VP in the maintenance of LTP in excitatory transmission in the LS. It is conjectured that the effects of VP on LS neurons are related to the role of the peptide in the maintenance of LTP and that these processes play a role in memory formation.