A new operative approach has been designed for the relief of medically intractable focal epilepsy. It is intended particularly to be used in those cases where the epileptogenic lesion lies in "unresectable" cortex; that is, those cerebral regions subserving speech, memory, and primary motor and sensory function. The procedure is based upon experimental evidence indicating 1) that epileptogenic discharge requires substantial side-to-side or horizontal interaction of cortical neurons, and 2) that the major functional properties of cortical tissue depend upon the vertical fiber connections of the columnar units. The technique requires severing of tangential intracortical fibers while preserving the vertical fiber connections of both incoming and outgoing nerve pathways and of the penetrating blood vessels which also have a vertical orientation. In this study, the effect of multiple subpial transection was assessed on both function and seizure control. The effect on function was reviewed in 32 cases; only 20 cases were evaluated with respect to seizure control, since a follow-up period of 5 years or more (5 to 22 years) is required before conclusions can be drawn. Multiple subpial transection was applied to the precentral gyrus in 16 cases, the postcentral gyrus in six, Broca's area in five, and Wernicke's area in five. With respect to function, the major finding was that none of the 32 patients has suffered a clinically significant behavioral deficit (although subtle deficits could be detected by careful neurological examination). Complete control of seizures has been obtained in 11 (55%) of the 20 cases evaluated. Nine patients developed recurrent seizures consequent to progressive disease unsuspected before operation (Rasmussen's encephalitis in five, tumor in three, and subacute sclerosing panencephalitis in one). In none of these cases, however, did the recurrent seizures arise in the transected zone. Thus, the results indicate that multiple subpial transection is about as effective as standard excisional therapy, and can be successfully employed when epileptogenic lesions encroach upon cortical territories, the removal of which would be functionally incapacitating.