Cerebral cortical dysgenesis (CD), as revealed by MRI, is the second commonest cause of medically refractory chronic partial epilepsy. Surgical treatment is often disappointing in these cases. This has been attributed to the probable diffuse nature of the condition but proof of this in the human brain is lacking. We have quantitatively analysed MRI scans of 30 neurologically normal control subjects and 18 patients with CD, examining the regional distribution of grey and subcortical matter volumes. In 15 out of the 18 patients, we have demonstrated abnormalities of this distribution beyond the margins of the visualized lesion. Nine out of 10 patients with dysgenetic lesions visualized only in one hemisphere had volumetric abnormality in the apparently normal contralateral hemisphere. These abnormalities were not visible on reinspection of the MRI scans. Such abnormalities were not found in 10 patients with isolated hippocampal sclerosis (HS) although the history of generalized seizure activity and duration of epilepsy did not differ between the two groups of patients. Thus there is evidence for the existence of extensive structural disorganization outside visually identified focal lesions in the brains of patients with CD and chronic partial epilepsy. This disruption is not due to the effects of the epilepsy and must instead be associated with its cause. Possible mechanisms producing the abnormalities are discussed. The methodology described may be applied to other cortical diseases.