This is a report of two brothers iwth mucopolysaccharidosis. The 8- and 10-year-old boys presented the characteristic clinical symptoms of the syndrome in their entirety. Both had a highly increased excretion of heparan sulfate in urine. The elder boy died and was autopsied and diagnosed as having Sanfilippo disease Typ A by a drastic reduction of heparan sulfate sulfamidase activity in organ extracts. Histochemically, highly water-soluble, sulfate acid mucopolysaccharides were demonstrated in liver, spleen, and cerebrum of the deceased child. Chemical analyses revealed a 12-fold increase of sulfated mucopolysaccharide in the patients liver and a 4.5-fold increase in the cerebrum when compared with normal controls. The sulfated polysaccharide consisted mainly of heparan sulfate, which was of low molecular size, heterogeneous in charge, and rich in its sulfamino hexose content. In addition, the gangliocytes of cerebrum and cerebellum had accumulated glycolipids. Electron microscopically the storage cells were overloaded with lysosomal residual bodies. The mitral valve was also involved in the storage process, which is a rare manifestation of the Sanfilippo syndrome. Acid mucopolysaccharides were deposited intracellularly as well as extracellularly in the mitral valve tissue. Polarisation microscopically there was found a change from normally positive to negative birefringence in the connective tissue ground substance of the mitral valve when containing stored mucopolysaccharides.