Enzymic and lipid studies were performed in two dogs with globoid leukodystrophy (GLD) and appropriate controls. One GLD dog was of the Westhighland Terrier strain, the other was of the Cairn Terrier strain. Both dogs consistently showed a β-galactocerebrosidase deficiency. The activity of this enzyme was markedly reduced both in the central nervous system, liver, and kidney. In contrast, the less specific paranitrophenyl galactosidase assays did not clearly differentiate the GLD dogs from their controls. Slightly low β-galactocerebrosidase activities were also found in one quite healthy littermate. The data suggest that this dog was a seemingly normal heterozygote carrier of GLD. Enzyme systems concerned with the metabolism of sulfatide were also studied. There was a slight reduction in lipid sulfotransferase activity in cerebral white matter and cerebellum, but not elsewhere. Sulfatase A, other sulfatases, and acid phosphatase activities showed no consistently distinctive abnormalities. Lipid assays of GLD cerebral white matter revealed a slight reduction in total lipid, a slight increase in cerebroside, and a slight decrease in sulfatide. There was no elevation in cerebroside in cerebral white matter of the dog who appeared to be a heterozygote carrier. The β-galactocerebrosidase deficiency of these GLD dogs, taken together with the deficiency of this same enzyme in human GLD, suggests that the canine disorder is an authentic enzymic model of the human disease.