White matter signal hyperintensities (WMSH) are commonly seen on MRI of elderly subjects. The purpose of this study was to characterize metabolic changes in the white matter of elderly subjects with extensive WMSH. We used water-suppressed proton (1H) magnetic resonance spectroscopic imaging (MRSI) to compare six subjects with extensive WMSH with eight age-matched elderly subjects with minimal or absent WMSH, and phosphorus (31P) MRSI to compare nine subjects with extensive WMSH and seven age-matched elderly subjects without extensive WMSH. Relative to region-matched tissue in elderly controls, extensive WMSH were associated with increased signal from choline-containing metabolites, no significant change of signal from N-acetylaspartate, and a trend to a decreased phosphomonoester (PME) resonance. These findings suggest that WMSH may be associated with an alteration of brain myclin phospholipids in the absence of axonal damage. There were no differences in energy phosphates, consistent with lack of ongoing brain ischemia. Within the group with extensive WMSH, PME resonance measures were significantly lower in WMSH than in contralateral normal-appearing white matter. These results provide information on pathophysiology of WMSH and a basis for comparison with WMSH in Alzheimer's disease, vascular dementia, multiple sclerosis, and other diseases.