31P Magnetic resonance spectroscopy of the frontal lobe was performed in 17 patients with Alzheimer's disease (AD), 8 elderly controls (EC), and 17 young controls (YC). The phosphocreatine/inorganic phosphate (PCr/Pi) ratio in AD (2.32 +/- 0.26 SD) was significantly lower than in EC (2.65 +/- 0.41). In AD patients, a correlation was observed between the PCr/Pi ratio and the dementia rating scale (r = -0.50, p = 0.04). A significant positive correlation between PCr/Pi ratio and age was observed in both AD (r = 0.67, p = 0.003) and YC (r = 0.63, p = 0.006) groups, however, suggesting caution in interpretation of this ratio in AD. We did not find differences between AD, EC, or YC in any other spectroscopic measure. A significant sex difference in the phosphomonoester/phosphodiester ratio (PME/PDE) ratio was observed in AD brain. Females had a lower PME/PDE ratio than males.