Ultrastructural and biochemical studies were performed on biopsy and postmortem tissue from a 22-year-old woman with generalized seizures and intellectual and behavioral deterioration. Her symptoms began at age 18 and, during the last year of life, normal-pressure hydrocephalus was demonstrated. Abnormal accumulation of granular periodic acid-Schiff (PAS)-positive material was found in the cytoplasm of cells of both brain and spleen. Numerous membrane-bound, multilamellar cytoplasmic inclusions were seen in cells of the brain, spleen, and arachnoid granulation. Tissue concentrations of lipid-bound sialic acid were 38 percent greater than age-matched control specimens. A marked increase of only the GM2 ganglioside was demonstrated by thin-layer chromatography. An eightfold increase in the quantity of GM2 ganglioside was found in the cerebral cortex. Total hexosaminidase activity was increased 85 percent, associated with an increase in the activity of both hexosaininidase A and B, resembling an adult onset form of the “AB variant” of GM2 gangliosidosis.