1. In cats, rabbits and monkeys, single cortical shocks can reduce the excitability of cortical neurones for 100-300 msec; the inhibitory effect is readily demonstrated, even in previously quiescent cells, against a background of activity evoked with small amounts of L-glutamate, released from an extracellular recording micropipette by iontophoresis.2. Other forms of cortical activity are also inhibited in a similar way by direct or indirect cortical stimulation; they include single unit discharges produced by iontophoretic applications of ACh or by a cathodal current, spontaneous discharges, and slow wave activity, both spontaneous and evoked.3. Most stimuli which elicit cortical activity also evoke some inhibition in the cortex, for instance, transcallosal volleys, and thalamic or peripheral shocks. In each case, a characteristic, prolonged depression is produced by single shocks.4. The most effective stimuli are direct cortical shocks, especially when applied within the cortex, below a depth of 0.6 mm; surface cathodal shocks are more effective than anodal shocks. These stimuli do not first excite the cells which are inhibited and they are not strong enough to cause appreciable local injury.5. Because of its long duration, the inhibition is often readily maintained by repetitive stimulation at frequencies of 5-7/sec. A cumulative effect leads to a further silent period after the end of stimulation; this increases with the strength, frequency and duration of the tetanus, so that after stimulation at 50-100/sec, the silent period may last for over 1 min. During this time, a stronger depolarizing stimulus can initiate firing.6. The inhibitory effect is often preceded and followed by phases of increased excitability; these may also show cumulative enhancement during repetitive stimulation, and a high frequency tetanus often leads to a short after-discharge, which is then followed by a long silent period, as above. Comparable changes take place in rabbits during spreading depression.7. The inhibitory effect of a direct shock can spread over an area covering 1 cm of cortical surface, affecting the cells through all cortical layers; but the spread is uneven in different directions, being particularly poor under most sulci.8. This type of inhibition can be elicited in all areas of the neocortex, and it is evident in kittens within a week of birth.9. Antidromic pyramidal stimulation is very much less effective in evoking inhibition of Betz cells, and other cortical neurones, than direct cortical stimulation; the inhibition by direct shocks is therefore not likely to be mediated through pyramidal excitation.