To determine characteristic MR imaging features of Zellweger syndrome.Clinical records, laboratory records, and MR studies of six patients with Zellweger syndrome were reviewed retrospectively. MR studies were examined for the state of myelination; the presence, extent, and morphologic appearance of cerebral cortical anomalies; the status of the cerebellar cortex, basal nuclei, and brain stem; and the presence or absence of any regions of abnormal signal intensity.The diagnosis of Zellweger syndrome was established in all patients by clinical findings combined with laboratory and MR results. All patients had impaired myelination and diffusely abnormal cortical gyral patterns that consisted of regions of microgyria (primarily in the frontal and perisylvian cortex) together with regions of thickened pachygyric cortex (primarily perirolandic and occipital). The pachygyric regions were in the form of deep cortical infoldings. Germinolytic cysts were visible in the caudothalamic groove in all patients, seen best on coronal or sagittal T1-weighted images. One patient had T1 shortening in the bilateral globus pallidus, presumably related to hepatic dysfunction and hyperbilirubinemia.The combination of hypomyelination, cortical malformations that are most severe in the perisylvian and perirolandic regions, and germinolytic cysts are highly suggestive of Zellweger syndrome in the proper clinical setting.