Electrophysiological techniques were used to investigate the effect of stimulating the perforant pathway (PP) on pyramidal neurons in the CA1 region of the hippocampal slice. Stimulation of the PP evoked both field potentials and single unit discharges in the pyramidal cell layer of the CA1 region. Several lines of experimental evidence suggest that the CA1 response does not involve granule or CA3 neurons: (i) movement of the recording electrode in the CA1 region away from the site of stimulation in the PP and closer to the CA3 region increased the latency of the evoked potential; (ii) the sum of latencies of the individual pathways in a trisynaptic circuit - from the PP to granule cells to CA3 neurons to CA1 neurons - was 2-3 times longer than the latency of the PP evoked response recorded in the CA1 region: (iii) lesioning the mossy fiber pathway or excising the CA3 region did not inhibit the CA1 response to PP stimulation. Other experimental results suggest that the PP activation of CA1 pyramidal neurons involves a direct synaptic pathway: (i) PP stimulation evoked potentials with similar latencies in the dentate gyrus and the CA1 region; (ii) the CA1 response was abolished in a Krebs' solution containing low calcium/high magnesium; (iii) excising a portion of the CA1 region between the stimulating electrode in the PP and the CA1 recording electrode, but sparing the PP, did not abolish the CA1 response; (iv) electrolytic lesions of the PP abolished the CA1 response to PP stimulation, but did not affect the CA1 response to stimulation of the CA3 region. The data suggest that fibers in the PP make direct synaptic connection with pyramidal neurons in the CA1 region of the hippocampus.