Spongy degeneration of the brain, Canavan disease (CD; McKusick 27190) is an autosomal recessive leukodystrophy (van Bogaert and Bertrand, 1967). Recently, Matalon et al. (1988) have reported three children with CD who had excessive amounts of N-acetylaspartic acid (NAA) in urine, blood and brain, and deficiency of aspartoacylase (EC 3.5.1.15) in cultured skin fibroblasts and brain. We have expanded our studies to other children with CD and patients with leukodystrophies other than CD. In addition, we have purified aspartoacylase from human and bovine brain and studied the distribution of aspartoacylase and NAA in brain.