1. An in vitro slice preparation of rat prefrontal cortex was used to analyse the responses of layer V pyramidal cells to electrical stimulation of layer II. We also studied the long-lasting modifications of synaptic efficacy following high-frequency stimulation of the same region. 2. Stable intracellular recordings were obtained from forty-three regular spiking pyramidal cells. The input resistance was 56 +/- 18 M omega (mean +/- S.D.) at a resting membrane potential of -71 +/- 4 mV. 3. At rest, a single stimulus of increasing strength evoked a monophasic, purely depolarizing postsynaptic potential (PSP) of increasing amplitude. In neurons recorded with potassium acetate-filled micropipettes, membrane depolarization disclosed an excitatory-inhibitory (EPSP-IPSP) sequence (onset latency of the EPSP, 3.6 +/- 0.6 ms). 4. Superfusion with the non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the EPSP and suppressed the IPSP. The small EPSP which remained was blocked by the NMDA receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV). 5. In five cells, administration of 0.5 mumol l-1 bicuculline revealed a postsynaptic NMDA component in the evoked response as evidenced by its anomalous voltage dependence in the presence of Mg2+ and its sensitivity to APV. In these cells the latency of the APV-sensitive EPSP was the same as that of the APV-insensitive EPSP. 6. In six cells superfused with a high-Mg2+, low-Ca2+ artificial cerebrospinal fluid (ACSF) a small monosynaptic EPSP remained which had the same latency as the PSP recorded in control ACSF. 7. Patterned high-frequency stimulation (50-100 Hz) was applied to the afferents of twenty-eight neurons (twenty-three of them were recorded in the presence of bicuculline). During the train the membrane potential depolarized some 20 mV and each stimulus evoked a small PSP. The tetanic stimulation was followed by a short-term enhancement of the PSP amplitude and a slight increase in membrane input resistance. 8. Out of the twenty-eight cells, twenty-four showed long-lasting (over 30 min) modifications of the PSP. Long-term depression (LTD) of the evoked PSP was observed in fourteen cells and long-term potentiation (LTP) in ten cells. There was no significant change in the steady-state membrane properties and in the latency of the response. 9. In 64% of the cells that showed LTD and 70% of those that showed LTP of synaptic efficacy, the latency of the enhanced or depressed component of the PSP was the same as the control.(ABSTRACT TRUNCATED AT 400 WORDS)