Pathological and biochemical studies of two sibling cases (18-year-old girl and 16-year-old boy) with Sanfilippo syndrome type B are presented. Pathological study revealed distended neurons and neuronal processes with inclusions throughout the CNS and the visceral organs, and neuronal loss and corresponding gliosis. The authors paid particular attention to atrophic changes in the thalamus and to "dissociation gliomyélinique" in the cerebral white matter. Histochemistry and electron microscopy revealed regional differences in stored materials. Biochemical studies revealed an accumulation of glycosaminoglycans in the CNS and abnormalities in the lipid metabolism in the brain and visceral organs. A protein assay of the cerebrum showed increased glial fibrillary acidic protein and low levels of myelin basic protein in the white matter.