The purpose of this study was to characterize the proton magnetic resonance (MR) spectroscopic findings in the brains of patients infected with human immunodeficiency virus (HIV). Peak areas were used to calculate metabolite ratios. Spectra were analyzed by blinded readers who calculated areas under metabolite peaks. MR images were evaluated by blinded readers, with both white and gray matter being rated as normal or abnormal. An aggregate index that combined N-acetylaspartate/creatine (Cr), choline/Cr, and marker peak/Cr ratios resulted in mean scores for patients and control subjects of 4.4 +/- 1.5 (standard deviation [SD]) and 2.5 +/- 0.4, respectively (P = .001). Eight of 11 patients (73%) had abnormal MR images versus four of 11 control subjects. Thirteen of 15 patient spectra (87%) were abnormal (> 2 SDs from the mean of the control subjects), while only one of 10 control spectra was abnormal. These initial results indicate that proton MR spectroscopy is a potentially useful modality for detecting HIV involvement in the central nervous system.