PURPOSE: To differentiate intracranial lymphoma from Toxoplasma gondii lesions in patients infected with the human immunodeficiency virus, by means of localized spin-echo proton magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Twenty-seven lesions were studied (18 T gondii lesions, nine lymphoma lesions) at 1.5 T. Spectra were acquired at an echo time of 135 msec from voxels centered on the lesions. Both visual analysis and spectral fitting were used to obtain metabolite ratios for choline (Cho), creatine (Cr), N-acetyl (NA), lactate, and lipids. RESULTS: Three spectral categories were seen. One had large lipid peaks with suppression of other metabolites. Another had an elevated Cho/Cr ratio with relatively diminished NA. The third had features of the other two. Examples of each spectrum type were acquired from both T gondii and lymphoma lesions. Neither method of analysis allowed differentiation between lesion types. MR spectroscopy showed an overlap of spectra. CONCLUSION: The authors conclude that toxoplasmosis and lymphoma cannot be differentiated with spin-echo proton MR spectroscopy at 135 msec.