Vasopressin receptors are present in both the developing and mature dentate gyrus of the rat brain and are of the V1 vasopressor type. Because vasopressin has been shown to influence memory function when injected into the dentate gyrus, the influence of this peptide on an electrophysiological model of learning and memory using the field excitatory postsynaptic potential (EPSP) of the dentate gyrus was investigated. Results of these studies showed that nanomolar concentrations of [Arg8]-vasopressin induced a prolonged increase in the amplitude and slope of the evoked population response in the presence of 1.5 mM calcium. Moreover, the expression of the vasopressin-induced potentiation of the EPSP persisted following removal of vasopressin from the perfusion medium. The vasopressin-induced sustained increase has been termed long-term vasopressin potentiation (LTVP). The closely related neuropeptide oxytocin had no effect upon the EPSP of the dentate gyrus. Preincubation of hippocampal slices in a selective V1 antagonist blocked the expression of LTVP. The ability of the V1 antagonist to block LTVP demonstrates that the potentiation induced by vasopressin is receptor-specific. In the presence of 2.5 mM calcium, the effect of vasopressin was opposite to that observed in 1.5 mM calcium. Under the conditions of 2.5 calcium, vasopressin induced a prolonged depression in the amplitude and slope of the EPSP. Expression of both potentiation and depression appeared within 5 minutes of application and persisted for the length of the observation, 60 minutes. These experiments demonstrate that vasopressin can induce long-lasting changes in the excitability of dentate gyrus neurons that are both calcium-dependent and receptor-specific.