In refractory temporal lobe epilepsy (TLE) temporal lobe structures and functions are continuously or intermittently affected by abnormal brain electrical events, noxious neurochemical agents, and metabolic disturbances. There is conflicting evidence regarding the relationship between the duration of refractory mesial TLE and quantitative measures of temporal lobe functions and volumes of the hippocampi. Twenty patients (aged 28 +/- 7 years, 14 males) with an initial precipitating injury before the age of 5 years were subjected to high-resolution magnetic resonance imaging, fluoro-2-deoxy-d-glucose positron-emission tomography (PET), and the Wada test. We investigated whether the duration of unilateral refractory TLE (12 left, 8 right) affects hippocampal volume, glucose metabolism, or Wada hemispheric memory performance. Ipsilateral to the epileptogenic zone the hippocampal volume, metabolism, and Wada hemispheric memory performance were reduced compared to the corresponding contralateral measures. The duration of epilepsy controlled for age at investigation, side of seizure origin, underlying cause, and sex were negatively correlated with ipsi- and contralateral hippocampal volume, hippocampal metabolism, and Wada hemispheric memory performance. Moreover, ipsilateral Wada hemispheric memory performance and contralateral hippocampal glucose metabolism were correlated with the frequency of habitual seizures. Refractory TLE seems to be associated with a slow but ongoing bilateral temporal lobe damage. These cross-sectional results require verification by longitudinal studies carried out over a period of more than two decades.