Inherited defects in sphingolipid metabolism are associated with a number of disorders. A one mo. old male (JH) was first seen because of poor physical and motor development, frequent seizures, and an unusual appearance. The first child of young, unrelated Jewish parents, JH weighed 7 1bs. 12 oz. at birth after a normal 8 mo. gestation. He was limp and unresponsive, with coarse facies, macroglossia, gum hypertrophy, squat hands and feet, flexor contractures of the fingers, thickened loose hirsute skin, large inguinal hernia, enlarged liver and spleen and normal fundi. Death at 3 1/2 mo. followed a series of bronchopneumonic episodes. These features suggested GM1, gangliosidosis, which was ruled out by the finding of normal β-galactosidase activity in leukocytes and in a liver biopsy. The activities of acid phosphatase, β-glucosidase, β-N-acetylhexoseaminidase, α-fucosidase, α-mannosidase, and arylsulfatase A were greater than normal. The diagnosis of GM3 gangliosidosis was established by thin-layer chromatographic analysis, which demonstrated the accumulation of GM3 (N-acetylneuraminylgalactosylglucosylceramide) in post mortem samples of brain and liver. The enzymatic basis of the GM3 storage is now under investigation. (Supported in part by the John A. Hartford Fndn. and the Tay-Sachs Assn. of Maryland.)