Cerebral metabolic abnormalities in five children with infantile (1), late infantile (1), and juvenile (3) neuronal ceroid lipofuscinosis (NCL) were noninvasively assessed by localized proton magnetic resonance spectroscopy (MRS). Infantile NCL was characterized by a complete loss of N-acetylaspartate (NAA, neuronal marker), a marked reduction of creatines (Cr) and choline-containing compounds (Cho), and an elevation of myo-inositol (Ins, glial marker) and lactate (Lac) in both gray and white matter. Reduced NAA and elevated Lac were also detected in gray and white matter of late infantile NCL, but in this case not only Ins but also Cr and Cho were increased in white matter. In contrast to the infantile forms, juvenile NCL exhibited normal metabolic profiles. In one patient disease progression was indicated by reduced NAA and Cr in gray matter in a follow-up study after four years. The present findings in NCL are consistent with irreversible and generalized neuroaxonal loss as well as alterations of white matter glia similar to those found in leukodystrophies. The severity of metabolic disturbances correlates with clinical symptoms and decreasing age of onset.