At autopsy, we observed eosinophilic inclusions within the astrocytic cytoplasm in areas of polymicrogyria and heterotopic gray matter in a 17-year-old female with severe mental retardation and physical handicaps who had died of respiratory failure. The inclusions stained with acid fuchsin, azocarmine, Holzer's stain and phosphotungstic acid hematoxylin (PTAH). They reacted with anti-S-100 protein antibody. The cytoplasm of the astrocytes containing the inclusions reacted with antibody to GFAP. The inclusions were amorphous masses that consisted of aggregated clusters of osmiophilic coarse granules about 30 nm in diameter. Some rough endoplasmic reticulum was observed on the inside and outside of the inclusions and in the cytoplasm of the astrocytes lacking such inclusions. We suggest that these inclusions resulted from an abnormality at or near the rough endoplasmic reticulum.