To evaluate biochemical changes in contrast-enhancing multiple sclerosis (MS) lesions, we examined 14 patients with relapsing-remitting MS at acute clinical exacerbation with the help of contrast-enhanced magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopic imaging (1H MRSI). Using a 1.5-tesla MR system (Magnetom Vision, Siemens, Germany), we followed 29 contrast-enhancing and 24 nonenhancing MS lesions as well as normal-appearing white matter (NAWM) before and during high-dose methylprednisolone (HDMP) therapy. Metabolite ratios of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac) were calculated. A transient decrease in contrast enhancement under HDMP therapy was observed. Both groups of MS lesions showed significantly decreased NAA to Cr ratios compared to NAWM with no changes in time. Baseline 1H MRSI revealed significantly increased Cho to Cr ratios in the contrast-enhancing MS lesions (1.13 +/- 0.25) compared to the nonenhancing MS lesions (0.85 +/- 0.26, P < 0.001) and NAWM (0.97 +/- 0.22, P = 0.015). Both the contrast-enhancing and the nonenhancing MS lesions exhibited a significant increase in Cho to Cr ratios from the second to the third 1H MRSI. We identified resonances of lactate in both groups of MS lesions and NAWM without any significant group differences or changes over time. 1H MRSI provides additional information that help to estimate macrophages' activity, cell membrane activation, and neuronal impairment within MS lesions. We believe that combined contrast-enhanced MRI and 1H MRSI may help to further investigate inflammatory processes within active MS lesions and should be employed more frequently to the research on therapy effects in MS.