The exact nature of the relationship between Lewy body disease and Alzheimer's disease (AD) is unknown. To investigate this, we compared cases of pure Lewy body disease, mixed Lewy body disease with AD, and pure AD to see what pathological features were shared and how they differed. We counted neurons, Lewy bodies, diffuse and neuritic senile plaques, neurofibrillary tangles, and neuropil threads in the frontal and medial temporal cortex and hippocampus from 5 autopsied cases of Lewy body disease (without AD histopathology), 7 with combined Lewy body disease and AD, 6 with AD, and 5 age-matched normal control subjects. Average neuronal counts in the cases with Lewy body disease were indistinguishable from those of control subjects, but higher than those for AD and combined Lewy body disease and AD. Diffuse plaque densities were similar in all disease forms. Neuritic senile plaques, neurofibrillary tangles, and neuropil threads were numerous in AD and combined Lewy body disease and AD, but sparse or absent in Lewy body disease and controls. Pure Lewy body disease and AD appear to be distinct clinicopathological entities except for the common feature of diffuse plaques in both disorders.