To evaluate (1)H-MRS profiles of the putamen in presymptomatic and manifest Huntington's disease (HD) patients for spectroscopic markers that are reliable, consistent signs of early pathology and to look for hemispheric differences as signs of use activation in an accelerated degradative process of the dominant hemisphere. A short echo time Point RESolved Spectroscopy (PRESS) spectroscopic imaging study was performed at low field (0.5 Tesla, T) on 27 right-handed patients (17 presymptomatic gene carriers and 10 manifest patients of less than 3 years from clinical onset) and 10 right-handed normal volunteers. Spectra from individual voxels (0.56 cm(3)) in the putamen were selected for analysis. Resonance areas of peaks were normalized to water as a concentration standard. Interhemispheric comparisons were made in individuals in all three groups to look for hemispheric differences. Two presymptomatic patients showed normal spectra but all other HD patients displayed some combination of reduced N-acetylaspartate (NAA), enhanced glutamate/glutamine (Glx) activity, and lactate (Lac) elevations or reduced creatine (Cr). Rather than showing any one metabolite as pathognomonic of early change, spectroscopic profiles showed heterogeneity between HD patients. Low creatine was common in the presymptomatic but not in the manifest group. Hemispheric ratios of abnormal metabolites showed lower values of NAA and Glx in the dominant hemisphere in all three groups but values of creatine were selectively lower in the dominant hemisphere of only the presymptomatic patients. Lac was elevated in both hemispheres but less so in the dominant hemisphere in all HD patients. (1)H-MRS profiles from the putamen of presymptomatic and manifest patients reflect heterogeneity in pathophysiology. With the possible exception of low creatine in presymptomatic patients (1)H-MRS spectra are not suggestive of hemispheric differences supportive of an overall accelerated degradative process in the dominant hemisphere.