The present study tested the hypothesis that proton magnetic resonance spectroscopy (1H-MRS) predicted neurodevelopmental outcome in infants with cystic leukomalacia (CL). Nineteen infants with CL (grade 2, N = 7; grade 3, N = 7; grade 4, N = 5), graded according to the authors' classification, were examined at corrected ages of mean 1.5 +/- 2.1 SD weeks. 1H-MRS of the basal ganglia and the periventricular white matter was performed. Two infants died, 16 had an adverse neurodevelopmental outcome and one was normal at follow-up. N-acetylaspartate (NAA):choline (Cho) ratios were mean 1.12 +/- 0.19 (SD) (grade 2), mean 0.95 +/- 0.11 (SD) (grade 3), and mean 0.71 +/- 0.13 (SD) (grade 4). These differences are significant (P < 0.01, ANOVA). NAA:Cho ratios showed a positive correlation with developmental quotient (DQ) at the age of > or = 1 year (P < 0.05). In 13 infants lactate (Lac) was found. Lac:NAA ratios showed a negative correlation with NAA:Cho ratios, but not with DQ. We conclude that a low NAA:Cho ratio predicted a poor outcome, whereas some infants developed unfavourably despite a normal NAA:Cho ratio. We speculate that partial volume effects might explain this observation.