UNLABELLED Labelle M, Khiat A, Durocher A, et al. Comparison of metabolite levels and water diffusion between cortical and subcortical strokes as monitored by MRI and MRS. Invest Radiol 2001;36:155-163. RATIONALE AND OBJECTIVES Proton magnetic resonance spectroscopy (MRS) and functional imaging techniques are increasingly recognized as useful tools for the characterization of strokes. The aim of this study was to compare cortical and subcortical (lacunar) strokes by MRS and diffusion-weighted imaging (DWI) experiments as a function of time. METHODS Single-voxel MRS, DWI, and perfusion-weighted imaging data were recorded on patients with cortical (n = 7) or subcortical (n = 7) strokes in the acute, subacute, and chronic periods. Magnetic resonance spectra were acquired in three regions: hyperintense DWI area, adjacent area with normal DWI intensity, and contralateral area. Neurological deficits were estimated by the National Institutes of Health Stroke Scale. RESULTS Decreases in N-acetylaspartate, choline-containing compounds, and creatine/phosphocreatine signal intensity as well as the presence of lactate were observed at all times in the hyperintense DWI area of all lesions. Small decreases were measured in the subacute and chronic phases for the adjacent area of cortical strokes but not for the adjacent area of subcortical strokes. The existence of a surrounding affected area in subcortical strokes is deduced from a combination of MRS and DWI results, possibly corresponding to the ischemic penumbra. Differences were found between the two types of lesion, especially an increased time variability of apparent diffusion coefficients in subcortical strokes. CONCLUSIONS Magnetic resonance spectroscopy provides evidence for the existence of affected tissue outside the hyperintense DWI regions in subcortical strokes. Cortical and subcortical strokes display different DWI and MRS characteristics.