Brain histopathology of 32 fetuses with Down syndrome was compared to that of 25 age-matched normal controls and 9 brains of fetuses of HIV positive mothers. Four cases of Down syndrome and 1 HIV case showed microdysgenesia of the cerebral cortex. As the pathogenetic background of cortical irregularities is presently not known, we analyzed the neuronal expression of drebrin, an actin-binding protein of neuronal dendritic spines. This protein is thought to play a role in synaptic formation and was recently shown to be manifold reduced in brains of fetuses with Down syndrome. However, immunocytochemistry revealed no differences in drebrin expression pattern between Down patients and controls. We conclude that cerebral cortical microdysgenesia is an infrequent non-specific pathology in fetal Down syndrome.