1. The spatiotemporal pattern of inhibition in the cat motor cortex was studied in in vitro slice preparations in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV). 2. After intracortical microstimulation (0.5-6 microA), fast and slow inhibitory postsynaptic potentials (IPSPs) were produced in layers II-VI pyramidal cells and selectively reduced with bicuculline methiodide and phaclofen, respectively. 3. Fast IPSPs were maximally produced by stimulation of the same layer where their cell bodies were located, and they decreased in amplitude as the more superficial layer was stimulated. In contrast, slow IPSPs were maximally produced by stimulation of layer II regardless of the location of the recorded pyramidal cell and decreased in amplitude as the deeper layer was stimulated. 4. The reduction of amplitude of fast IPSPs, in response to a vertical shift of the stimulation site toward more superficial layers, was always correlated with an increase in rise time and with a shift of the reversal potential to a more hyperpolarized level. 5. When the stimulation site was moved horizontally to the more lateral site, fast IPSPs increased in latency and decreased in amplitude gradually without appreciable changes in rise time. Fast IPSPs could be evoked from horizontally remote sites of up to 800-1,200 microns. 6. Inhibitory interneurons, which are responsible for evoking fast IPSPs, appear to be distributed through almost all layers to send horizontally spreading parallel axons making synaptic contacts at different electrotonic distances along apical dendrites of single pyramidal cells. 7. Horizontal spreads were much less in slow IPSPs (< 340-680 microns). The time-to-peak of slow IPSPs produced in layer V pyramidal cells (159.5 +/- 6.8 ms, mean +/- SD, n = 10) was significantly (P < 0.0001) longer than that in layers II and III pyramidal cells (128.5 +/- 7.5 ms, n = 7). Asymmetric reversal properties of slow IPSPs were seen, suggesting the spatial dispersion of synaptic inputs along apical dendrites of pyramidal cells. 8. In layer V pyramidal cells, the time-to-peak of slow IPSPs decreased with increasing membrane hyperpolarization, indicating that the later portion of slow IPSPs was more sensitive to the membrane-potential change than the early portion. This further indicates that the late portion of slow IPSPs is generated at synapses on the more proximal dendrite of pyramidal cells than the early portion, contrary to that expected from the Rall's model of passive dendrite under the condition of synchronous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)