Quantitative assessment of regional cerebral blood flow (rCBF) in the bilateral cerebral and cerebellar cortices was performed in 15 epileptic adult patients receiving chronic high-dose antiepileptic drug therapy and 22 normal volunteers matched for sex and age, using single photon emission computed tomography with N-isopropyl-(iodine-123)-p-iodoamphetamine. The entire averaged rCBF value in the epileptic patients, i.e. 52.8 ± 13.7 ml/100 g/min (range: 25-78 ml/100 g/min), was significantly lower as compared with that in the normal subjects, i.e. 69.1 ± 14.2 ml/100 g/min (range: 46-102 ml/100 g/min). Six of the 15 patients showed absolute rCBF values less than the minimum of the normal range, i.e. 46 ml/100 g/min, in all or most of the measured brain tissues. There was a significant correlation between the diffuse cerebral hypoperfusion and simultaneous ingestion of phenytoin and phenobarbital. The possible effects of antiepileptic drugs on rCBF are discusse