A sister and brother, now aged 7 and 9 years, presented with developmental arrest, gait disturbance, dementia, and a progressive myoclonic epilepsy syndrome with hyperacusis in the second year of life. Then, spastic quadriparesis led to a decerebrate state. In the absence of macular or retinal degeneration, organomegaly, and somatic-facial features suggesting mucopolysaccharidosis, the presence of hyperacusis together with sea-blue histiocytes in bone marrow biopsies and deficient β-galactosidase activity but normal glucosidase, hexosaminidase, and neuraminidase activity on lysosomal enzyme assays constitutes the clinical-pathologic-biochemical profile of G_M1 gangliosidosis type 2. This is a rare, late infantile onset, progressive gray-matter disease in which β-galactosidase deficiency is largely localized to the brain, though it can be demonstrated in leukocytes and cultured skin fibroblasts. It must be distinguished from the Jansky-Bielschowsky presentation of neuronal ceroid lipofuscinosis, mitochondrial encephalopathy, lactic acidosis, strokelike episodes (MELAS) and myoclonic epilepsy with ragged-red fibers (MERRF) syndromes, atypical presentations of G_M2 gangliosidoses (Tay-Sachs and Sandhoff's diseases), primary sialidosis (neuraminidase deficiency), galactosialidosis, and Alpers' disease. (J Child Neurol 1992;7(Suppl):S41-S50.)