In 76 normal volunteers studied by positron emission tomography, with [18F]fluorodeoxyglucose, CMRglu was significantly lower in the elderly as compared with young subjects and significantly higher in females relative to males. However, in 58 of these subjects who also had magnetic resonance imaging scans, age and gender were found to be unrelated to CMRglu, when the effects of brain volume and brain atrophy on CMRglu were partialed out using covariate analyses. Individually, brain volume was found to have a significant effect on CMRglu, explaining approximately 17% of the variability in CMRglu measures and brain atrophy explaining approximately 8% of the variance in CMRglu. Together these two measures accounted for approximately 21% of the variance. Cerebrovascular risk factors in normal subjects were not found to affect mean CMRglu or the variability of CMRglu measures. In this study almost 80% of the variance in CMRglu could not be explained by any of the factors that had been considered. This implies a lack of sensitivity of absolute values of global CMRglu to the mild effects of brain dysfunction. Although some of the unexplained variance is probably methodological in origin, physiological factors that are difficult to quantify, such as the state of arousal, are likely to be contributory as well.