The effect of the dopamine system on the induction of long-term potentiation (LTP) in the dentate gyrus was studied in anesthetized rats. A subthreshold tetanic train (seven pulses at 100 Hz) given to the perforant pathway, which usually fails to elicit LTP, potentiated a slope of field excitatory postsynaptic potentiation (fEPSP) measured from the hilus of the dentate gyrus when a precursor for catecholamine, L-3,4-dihydroxyphenylalanine (L-DOPA), was administered orally to rats. The increase in the fEPSP slope persisted for at least 60 min. Intraventricular injection of a specific dopamine D1/D5 agonist, SKF38393, mimicked the effect of L-DOPA, suggesting an involvement of D1/D5 receptors in the induction of dentate gyrus LTP. Consistent with this, intraventricular administration of the D1/D5 antagonist SCH23390 resulted in complete inhibition of LTP induction by a longer tetanus (100 pulses at 100 Hz), which usually elicits a robust LTP. Thus, D1/D5 receptor activation appears to modulate LTP induction in vivo.