Amplitudes of EPSPs evoked by repetitive presynaptic action potentials can either decrease (synaptic depression) or increase (synaptic facilitation). To determine whether facilitation and depression in the connections between neocortical pyramidal cells varied with the identity of the pre- or the postsynaptic cell and whether they changed during postnatal development, whole-cell voltage recordings were made simultaneously from two or three pyramidal cells in layers 2/3 and 5 of the rat sensorimotor cortex. Unitary EPSPs were evoked when pre- and postsynaptic neurons were in the same and in different layers. In young [postnatal day 14 (P14)] cortex, EPSPs evoked in all connected neurons depressed. The degree of depression was layer specific and was determined by the identity of the presynaptic cell. EPSPs evoked by stimulation of presynaptic layer 5 neurons depressed significantly more than did those evoked by stimulation of layer 2/3 neurons. In mature cortex (P28), however, the EPSPs evoked in these connected neurons facilitated to a comparable degree regardless of the layer in which pre- and postsynaptic neurons were located. The results suggest that in young cortex the degree of synaptic depression in connected pyramidal cells is determined primarily by whether the presynaptic cell was in layer 2/3 or 5 and that maturation of the cortex involves a developmental switch from depression to facilitation between P14 and P28 that eliminates the layer-specific differences. A functional consequence of this switch is that in mature cortex the spread of excitation between neocortical pyramidal neurons is enhanced when action potentials occur in bursts.