We investigated regional cerebral glucose metabolic rates (rCMRgluc) with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in 7 monozygotic twin pairs discordant for Alzheimer’s disease (AD). Ten healthy volunteers with comparable mean age and educational level served as controls. In the hippocampus, the mean ± SD rCMRgluc were 0.20 ± 0.03 µmol/ml/min for the demented twins, 0.21 ± 0.03 µmol/ml/min for their non-demented co-twins, and 0.23 ± 0.02 µmol/ml/min for the controls. The mean hippocampal rCMRgluc was reduced in the demented twins (p = 0.006), compared with the controls. In the lateral temporal cortex, the mean ± SD rCMRgluc were 0.27 ± 0.05, 0.28 ± 0.04, and 0.32 ± 0.02 µmol/ml/min, respectively. These mean rates were reduced both in the demented (p = 0.02) and the non-demented (p = 0.01) twins, compared with the controls. In conclusion, in the demented twins, the reduction of rCMRgluc was detected in the hippocampus and lateral temporal cortex, i.e. the 2 brain areas which show early changes in pathological and imaging studies in AD. Their non-demented co-twins showed milder reductions, which may be an indication of genetic susceptibility for dementia, and an early sign of a dementing illness in them.