Abstract During preoperative evaluation of epilepsy, drug-induced spike activation may be used to delineate the localization of the epileptogenic focus. We evaluated the usefulness of thiopental for the localization of the epileptogenic focus. Twenty-two patients (10 women, 12 men) aged 18–43 years (mean 29.6 years) underwent long-term EEG recordings with subdural strip and intra-hippocampal depth electrodes (SDSE, IDE). After consecutive intravenous (i.v.) administration of 200 and 375 mg thiopental (5 min apart), spike activation and suppression of preexisting spike activity were assessed quantitatively, and changes in drug-induced beta-activity were evaluated qualitatively. After 375 mg thiopental, 16 of 21 patients with SDSE and 17 of 21 patients with IDE showed a spike activation. In 9 of 16 patients with spike activation in the strip electrodes and in 8 of 17 patients with spike activation in the depth electrodes, the activation correlated with the region of ictal onset. Focal reduction of drug-induced beta-activity was noted in 6 patients, corresponding in 4 of them to the epileptogenic focus. In 9 patients, preexisting spike activity was suppressed. The results show that thiopental may provide complementary information as to the localization of the epileptogenic focus in only a limited number of patients.