Background and evoked neuronal activity in the cat sensorimotor cortex was recorded under a-chloralose anesthesia. Pairs of heterogeneous stimuli were applied, spaced at intervals of 0, 100, 200, 300, and 400 msec. A clicking sound, flashing light, and electroshock to the contralateral forepaw were used as stimuli. Partial or complete blockade of response to test stimuli presentations spaced 100–200 msec apart were observed when using stimulation of varying modality. The greatest test response was recorded at interstimulus intervals of 200–300 msec. Intracellular mechanisms of heterosensory interaction were investigated by applying the inhibitory transmitter antagonist picrotoxin microiontophoretically to the test cell to produce local attenuation of inhibitory effects. This substance also reduced the duration of blockage following the conditioning stimulus and the occurrence of peak level test response at a lower interstimulus interval than in the controls. Either a consistent increase in the number of spikes per response at one of the interstimulus intervals or a uniform reinforcement in unit response to several different interstimulus intervals were observed in a proportion of the cells. The contribution of intracortical inhibitory influences to the mechanisms of heterosensory interaction on neurons of the cat sensorimotor cortex is discussed in the light of our findings.