The usefulness of determining medial temporal lobe (MTL) size in differentiating Alzheimer's disease (AD) from other dementia subtypes is unknown. We compared the cross-sectional areas of the MTLs in histological sections from the brains of 18 patients with dementia with Lewy bodies (DLB) but lacking AD changes, 24 DLB patients with concurrent AD pathology, 20 pure AD cases, and 18 age-matched control cases. Duration and severity of disease were comparable between groups. When data for cross-sectional area were expressed as percentages of the average control area, DLB MTLs were significantly larger than either AD or DLB/AD MTLs at rostral levels (86 +/- 16%, 54 +/- 17%, and 66 +/- 23% of control areas, respectively). At caudal levels, DLB MTLs were larger than AD MTLs (80 +/- 20%, 59 +/- 21%, and 77 +/- 26% of control areas in DLB, AD, and DLB/AD, respectively). MTL cross-sectional area often approaches normal in pure DLB, even when disease duration is prolonged and symptoms are end stage. In contrast, a greatly reduced MTL area mitigates against the diagnosis of DLB, unless there are concurrent AD changes.