1. To compare the dynamics of synaptic transmission at different types of connection, dual intracellular recordings were made from pairs of neurones in slices of adult rat neocortex. Excitatory postsynaptic potentials (EPSPs) were elicited by single spikes, spike pairs and brief spike trains in presynaptic pyramidal cells and responses recorded in postsynaptic pyramidal cells and in interneurones. 2. Pyramid-pyramid EPSPs were strongly voltage dependent and this resulted in a range of paired pulse effects. At thirty-two of sixty-nine pyramid-pyramid connections, the 2nd EPSP was the same shape as the 1st, indicating minimal interaction between active synapses. In these thirty-two connections, paired pulse depression (PPD) was apparent (2nd EPSP integral 46 +/- 21% of the 1st, at 5-20 ms), which recovered within 60-70 ms. 3. In eleven additional pyramid-pyramid pairs, the 2nd EPSP was also the same shape as the 1st, but paired pulse facilitation (PPF, 149 +/- 32%) decaying within 50-60 ms was apparent. Even these connections displayed frequency-dependent depression, however, as 3rd EPSPs were smaller than 1st EPSPs at intervals < 100 ms. 4. At twenty-five pyramid-pyramid connections, 2nd EPSPs were broader than 1st EPSPs and in sixteen of these, voltage- and NMDA receptor-dependent enhancement was large enough to obscure the underlying PPD. PPD was revealed by postsynaptic hyperpolarization (4 pairs), N-methyl-D-aspartate (NMDA) receptor blockade (3 paris), or if Mg2+ was removed (in the one case studied). If synapse location allowed significant depolarization of one active site by another, voltage-dependent enhancement could produce supralinear EPSP summation and overcome PPD. Third EPSPs were, however, consistently smaller than 1st EPSPs. 5. In striking contrast, profound frequency-dependent facilitation, independent of voltage or NMDA receptors was seen at fifteen connections involving two classes of postsynaptic interneurones. 6. At these pyramid-interneurone connections, facilitation of the 2nd EPSP (655 +/- 380% at 5-20 ms) decayed rapidly, within 50-60 ms. Third and fourth EPSPs showed additional facilitation which decayed more slowly, within 90 ms and 2 s, respectively. Facilitation due to five to six spike trains was still apparent at 3 s. Therefore, once initiated by a brief high frequency spike train, facilitation was maintained at lower frequencies.