The objective of this study was to determine whether cerebrospinal fluid(CSF)-corrected concentrations of N-acetylaspartate are lower in several brain regions of drug- and medication-free subjects with bipolar disorder as compared with matched healthy controls. Bipolar subjects (n=21) and age- and sex-matched healthy control (n=21) were studied using proton magnetic resonance spectroscopic imaging on a 3T magnetic resonance (MR) scanner. Spectra were quantified using the LCModel, and metabolite values were CSF-corrected to yield metabolite concentrations. Fourteen regions of interest and five metabolite concentrations in each subject were selected for statistical analysis. We found that bipolar subjects had significantly decreased N-acetylaspartate concentrations in both caudate heads and the left lentiform nucleus. Choline and creatine in the head of the right caudate were also significantly decreased in bipolar subjects. Significantly increased myo-inositol was found in the left caudate head in bipolar subjects. Bipolar subjects showed significantly decreased glutamate/glutamine concentrations in the frontal white matter bilaterally and in the right lentiform nucleus. No differences were found for other metabolites examined. These preliminary findings suggest decreased neuronal density or viability in the basal ganglia and neurometabolic abnormalities in the frontal lobes of subjects with bipolar disorder.