Magnetic resonance spectroscopy (MRS) in a non-invasive technique that permits estimation of brain metabolites in anatomically localized regions of interest. This method is attractive because it provides information regarding the intracellular environment of brain gray and white matter regions. In vivo investigations utilizing proton MRS yield metabolites with strong singlet characteristics: N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr), and at shorter echo times myo-Inositol (mI). Previous studies in individuals with HIV infection have noted declines in NAA which have been correlated with degree of dementia. Elevated Cho and mI have also been noted and likely represent development of gliosis. In regard to the CNS effects of stimulants, only three studies utilizing MRS have been reported; two studies of methamphetamine found altered phospholipids and monoesters using phosphorus MRS; and one proton MRS study of abstinent cocaine abusers found an increase in absolute Cr. Given the possibility that common excitotoxic mechanisms in fronto-striatal regions may underlie subcortical gray and white matter injury induced by HIV and methamphetamine, we intend to compare proton MRS data in four groups cross-sectionally and longitudinally; 80 HIV infected/methamphetamine dependent (HIV+/METH+); 50 HIV uninfected/methamphetamine dependent (HIV- /METH+): 40 seropositives who are not substance abusers (HIV+/METH-); and 20 seronegative non-drug using controls (HIV- /METH-). We predict that both HIV+ and METH+ will show reductions in NAA and increases in mI and Cho in fronto-striatal regions consistent with neural injury and gliosis, but that HIV+/METH+ will show the most marked changes suggesting an addictive effect of these two influences. We predict that lower NAA levels in fronto-striatal structures (indexed in our study by anterior cingulate gyrus, anterior centrum semiovale, and caudate nucleus) will relate to poorer neuropsychological performance and that these relationships will be mediated in part by severity and recency of substance use. We also predict that lower NAA and higher Cho and mI will be associated with indices of atrophy from MR morphometry, and in those participants who die, reductions in neuronal number and synapto-dendritic complexity.