Magnetic resonance spectroscopy (MRS) gives the opportunity to study in vivo, separately, gray matter and white matter neurochemical characteristics of Alzheimer's disease (AD) and to correlate metabolite alterations with measures of clinical severity. We carried out the present investigation performing proton spectroscopy (1H-MRS) in both gray and white matter of AD patients and age-matched controls. Twelve patients (2M, 10F, mean age 73.6+/-6, range of age 62-83 yr) consecutively referred to our Aging Brain Centre, fulfilling the NINCDS-ADRDA criteria for probable Alzheimer's disease entered the study. The degree of cognitive impairment, evaluated by Mini Mental State Examination, ranged from mild (MMSE score: 23) to severe (MMSE score: 4). Seven subjects (2M, 5F, mean age 70.4+/-15, range of age 51-92 yr) selected from among relatives or caregivers of demented patients were studied as control group. All of them had a clinical history negative for any neuropsychiatric disorder or other relevant pathologies and scored > 26 at MMSE. Neither patients nor controls were taking any drug at the time of observation. 1H-MRS was carried out using stimulation echo acquisition mode pulse sequence (TE=35ms; TR=2600 ms; band width 2500 Hz) on a 1.5 whole-body scanner (GEMS, Milwaukee, WI, USA). Quantification of metabolites (N-acetyl-aspartate, NAA; myo-inositol, mI; creatine and choline) was made referring the peak area to unsuppressed water peak and the ratio was expressed in arbitrary units. In AD group, both gray (6.43+/-0.61 vs 7.51+/-0.13, p<0.001) and white (7.56+/-0.66 vs 8.28+/-0.57, p=0.05) matter NAA concentration was significantly reduced as compared to controls; gray matter mI was higher in AD patients (4.53+/-0.86 vs 3.78+/-0.29, p<0.02). The ratio NAAmI in gray matter magnified the differences between groups (1.46+/-0.26 vs 2.00+/-0.16, p<0.001) without any overlap (range in AD group: 0.94-1.60; range in controls: 1.82-2.24). Finally, the relationship between neurochemical (mI, NAA, NAAmI) and clinical (MMSE score and duration of disease) parameters was assessed. White matter mI showed a significant association with duration of disease (r 2 =0.50, p<0.025). Age did not show any influence on the metabolites considered. These results, if confirmed in larger studies, can have clinical relevance, showing the positive contribution given by 1H-MRS in clinical diagnosis of AD.