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The purpose of our study was to determine whether proton magnetic resonance spectroscopy (MRS) could detect early brain involvement by human immunodeficiency virus (HIV). We recruited 19 asymptomatic HIV-infected patients, 9 with and 10 without a history of intravenous drug use (IDU), as well as 10 control subjects. All subjects had to have normal MR imaging to be enrolled. We identified the following peaks on proton MRS: n-acetyl aspartate, creatine, choline, and a conglomerate amino acid peak between 2.1 and 2.6 parts per million that we call the marker peaks. Proton MRS was able to demonstrate a statistically significant difference between HIV-infected subjects and controls. The marker/Cr was the best ratio to separate patients from controls, with controls having a mean ratio of 0.50 +/- 0.51 and patients having a mean ratio of 1.8 +/- 0.85 (p = 0.001). There was no difference between HIV-infected subjects with and without a history of IDU. No significant relationship was found between either neuropsychological test scores or CD4 count and metabolite ratios. In brief, MRS seems more sensitive than magnetic resonance imaging (MRI), being able to detect abnormalities in HIV-infected patients when imaging is normal.