The goal of the current study was to determine whether Alzheimer's disease (AD) pathology affects the limbic system of men and women differently as measured by in vivo neuroimaging. Magnetic resonance imaging (MRI) and coregistered single photon emission computed tomography (SPECT) were used to examine the limbic system in 20 men and 20 women with probable AD compared to 40 age- and education-matched normal controls (20 men, 20 women). Limbic volumes and relative perfusion values were obtained from the MR images and coregistered SPECT scans, respectively. No significant differences were found between sexes in limbic volumes or relative perfusion values in the normal controls. Many limbic regions were significantly affected in both men and women with AD compared to normal controls. However, only the men with AD displayed atrophy in the orbitofrontal cortex, middle and posterior cingulate cortices, hypothalamus, and mamillary bodies, and relative hypoperfusion in the anterior and middle cingulate cortices. Women with AD exclusively showed anterior thalamic atrophy. Separating men and women did not substantially improve diagnostic classification.