The objective of this study was to analyse the clinical characteristics, pathological features and expression patterns of multiple drug resistance type 1 (MDR1) and glial fibrillary acidic protein (GFAP) in intractable epilepsy patients with variable aetiologies and to analyse the relationships between the clinical and pathological findings. Twenty-six patients (15 males, 11 females, age range 4-25 years, mean age 22.92 years, SD 11.19 years) with intractable epilepsy were included in this study; the clinical characteristics were considered, and the pathological changes as well as expression of MDR1 and GFAP in surgically removed brain tissues of each subject were examined under light and electron microscopy. All patients presented a long-lasting, refractory epilepsy, mostly of the partial type, due to different causes, such as trauma, vascular injuries, encephalitis, cortical dysplasia, cavernous angioma and Sturge-Weber disease. Neuronal degenerative damage, reactive proliferation of astrocytes, as well as overexpression of GFAP and MDR1, appeared as common pathological features in all cases. The detection of MDR1 by electron microscopy allowed us to precisely define its cellular location in reactive astrocytes and to exclude the presence of the antigen in other cellular types. In all cases, pathological features, at both light and electron microscopy, were similar, independent of the different clinical presentation and aetiology.