The apolipoprotein E (APOE) gene epsilon 4 allele is known to be associated with late-onset familial and sporadic Alzheimer's disease (AD). We assessed the possible relationship between APOE genotypes and morphological or functional changes in AD brains by x-ray computed tomography (CT), magnetic resonance imaging (MRI) and Xe-133 single photon emission CT (SPECT). First, we estimated the change in size of the whole brain and total ventricular system by using two x-ray CT indices, the cerebral index (CI) and ventricular index (VI), respectively. Neither CI nor VI differed significantly among APOE genotypes. Then, we focused on the inferior temporal lobe regions by introducing new MRI indices, the inferior temporal index (ITI), temporal horn index (THI) and infero-medial temporal index (IMTI). We found a significant difference in each MRI index among APOE subgroups; ITI and IMTI were lower, while THI was higher in AD patients with at least one APOE epsilon 4 allele (epsilon 4+ group) than in those without such an allele (epsilon 4-group). Finally, we compared relative regional cerebral blood flow (rCBF) of Xe-133 SPECT among the AD subgroups. Relative rCBF in the cerebral cortex, particularly in the temporal lobe, was lower in the epsilon 4+ group than in the epsilon 4- group. These results indicate that possession, and thus expression, of the APOE epsilon 4 allele affects preferentially the inferior temporal lobe, encompassing the hippocampus and amygdala, in AD patients.