We used a computerized image-analysis system to perform a quantitative analysis of rapid Golgi-impregnated pyramidal neurons of the third cortical layer of histologically normal cerebral cortex surgically removed from patients with partial epilepsy. Various parameters of 51 neurons from 9 patients and 29 neurons from 5 age-matched controls were compared. Dendritic spine density decreased progressively with increasing duration of seizures, and dendritic swellings were most numerous in epilepsy cases of uncertain etiology and in patients with seizures of longer standing. Neurons from seizure cases showed fewer dendritic branching points and fewer proximal dendritic branches than those from controls, suggesting a simplified dendritic architecture. These findings indicate that neurons in cortex distant from the primary site of epileptogenic activity may be undergoing subtle, progressive degeneration, which may explain the propensity of chronic epilepsy patients to have increased seizure activity and interictal behavioral and cognitive aberrations.