The Twitcher is a new neurological mutant of mouse which shows clinical and histopathological features similar to those of human and canine globoid cell leukodystrophy (Krabbe disease). Brain and liver tissues of affected mice showed a profound deficiency of galactosylceramidase and lactosylceramidase I activities. A distinct group with intermediate enzyme activities could be identified among the phenotypically normal mice, consistent with their being heterozygotes. The Twitcher mouse is, therefore, not only a clinically and morphologically, but also an enzymatically, authentic model of human globoid cell leukodystrophy. This is the first enzymatically authentic murine model of human sphingolipidosis.