Single-pulse stimulation of the perirhinal cortex (PRC) evoked field responses in the dorsal hippocampal CA1 region in urethane-anesthetized rats. In depth profiles conducted by moving the PRC stimulating electrode, the largest amplitude hippocampal potential was generated when the stimulating electrode was located within the perirhinal region. More dorsal (temporal cortex) or more ventral (lateral entorhinal cortex) stimulating sites elicited minimal hippocampal potentials. The hippocampal response was maintained during 100 Hz stimulation of the PRC, suggesting that it was monosynaptic, and high-frequency stimulation (400 Hz) of the PRC produced a significant potentiation of hippocampal CA1 field potentials (46.73 +/- 4.14%). When the PRC and the lateral perforant path (LPP) were stimulated separately, the depth/amplitude profiles obtained from a roving recording electrode located within the dorsal hippocampus were similar. In order to determine if fibers from PRC project to the hippocampus via the LPP, the PRC-CA1 and LPP-CA1 potentials were recorded prior to and during procaine (20%, 0.5 microliter) blockade of the LPP. A simultaneous loss of both potentials was observed immediately following procaine infusion, while a commissural control potential was unaffected. Both LPP and PRC potentials returned approximately 30-40 min later. Electrolytic lesions of PRC produced a significant decrease in the amplitude of LPP-hippocampal potentials when testing was conducted 4-5 days postlesion. Lesions of lateral entorhinal cortex or temporal cortex did not produce such effects. These data suggest that a direct pathway from perirhinal cortex to the dorsal hippocampal CA1 field can undergo long-term potentiation (LTP) and that this pathway makes a major contribution to the lateral perforant path.