The effects of (i) neural isolation of large bilateral cortical slabs with intact callosal connections, and (ii) of large unilateral subtotal thalamectomies associated with transection of the interhemispheric commissures on the generalized epileptiform discharges of generalized penicillin epilepsy of the cat were studied. Cortex devoid of subcortical, particularly thalamic, inputs was incapable of generating the characteristic 3.5- to 5-cycles/s epileptiform bursts of feline generalized penicillin epilepsy either in response to the i.m. injection of a large dose of penicillin or to the diffuse direct cortical application of a dilute penicillin solution. Such deafferented cortex, however, produced, even without penicillin, widespread often highly synchronized epileptiform discharges of a different kind consisting at times of slow, 1- to 2.5-cycles/s spike and wave complexes. This epileptiform activity increased in response to i.m. penicillin injection or to widespread direct cortical application of a dilute penicillin solution, but never assumed the characteristics of the typical discharges of feline generalized penicillin epilepsy as seen in cortex which has retained its subcortical connections. The discharges differed from those of intact cortex by being slower in frequency and less prone to become organized in bursts. In the bilateral slab preparation with preserved callosal connections, these atypical discharges occurred, however, in a bilaterally synchronous manner, as did the typical discharges in the intact cat with generalized penicillin epilepsy. This suggests that the corpus callosum is necessary for the bilateral synchrony of both types of epileptiform discharges. © 1979.