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Objective Multiple subpial transection (MST) is one approach to the surgical treatment of intractable epilepsy with epileptogenic lesion located in functional areas. To verify the effect of MST, an experimental study was performed first, followed by clinical application.rnMethods On the basis of the experimental study, MST was performed in 200 intractable epileptic patients from 1991 to 2000. Of them, 80 cases underwent MST only while 120 others underwent MST combined with other techniques, such as corpus callosotomy, temporal lobectomy and focus resection. A series of modifications of the surgical techniques were made.rnResults The results of the experimental study indicated that MST could inhibit the formation and spreading of epileptic discharge and limit the damage to neurons in a minimal area on the epileptogenic agent injected cortex. MST does not impair major functions of the cortex. After the clinical application and modifications, 160 patients were followed up for 1 to 8 years. Complete control of seizure was obtained in 100 cases (62.5%), significant reduction (more than 75%) in 32, reduction (more than 50%) in 20 and no change in 8. The total rate of effectiveness was 95.0%, and the significant rate of effectiveness was 82.5%. No functional defects were found in any patients. rnConclusions The results indicate that MST is an effective approach to the surgical treatment of intractable epilepsy. MST can be combined with other approaches. The outcome of the subdivision of the MST only group indicates that MST on local epileptogenic lesion without structural changes is as effective as that of the combined operation group. To evade hemispheric disturbance, MST should be done first to avoid severe complications. Hemispherectomy should be performed only on poor effected cases of MST.