Post-mortem studies on a 6-year old boy with GM1-gangliosidosis, Type II revealed no evidence of accumulation of residual bodies nor of gangliosides or glycoproteins in liver and spleen. In brain tissue the ganglioside GM1 accounted for 70% of the ganglioside fraction and ganglioside-NANA was increased 3.6 fold over controls. In addition, the brain tissue contained large amounts of glycoprotein, glycoprotein derived galactose being increased 2.5 times. The neuronal accumulation of tertiary lysosomes exhibited a characteristic distributional pattern: in general the large neuronal perikarya were more consistently involved with the exception of the motor cells of the cranial nerve nuclei, III, IV, and VI. In addition to characteristic MCB's, the nerve cells contained residual bodies with a granulo-floccular matrix, presumed to represent glycoproteins. The distribution of the mutant gene was studied among 30 blood relatives of the proband at risk and 6 carriers could be ascertained on the basis of a reduced leukocytic β-galactosidase activity. The partly purified enzyme from the patient's liver revealed 20% activity as compared to that of normal controls. All three fractions obtained by DEAE cellulose column chromatography exhibited markedly reduced activity at pH 3.6, but nearly normal activity at pH 6.6. The reduced activity corresponded to the B component of the enzyme as shown by electrophoretic separation. It is pointed out that this case cannot be diagnosed as “generalized gangliosidosis” for the process of ganglioside accumulation was restricted to nervous tissue.