Histologic changes in brains from mentally retarded patients are often subtle and may be limited to abnormalities in the dendritic and synaptic organization of the cerebral cortex. Special methods may be necessary for their demonstration. This review summarizes data on dendritic and synaptic pathology in human mental retardation syndromes. Findings in humans are compared to those in animal models that are of relevance to human disorders. Both in humans and in animal models there is evidence that development modifies the observed changes and that findings differ depending on the developmental age at which the tissue is studied.