The relationship between Alzheimer's disease (AD) and Lewy body disease (LBD) is poorly understood. In AD there is severe loss of neurons comprising the perforant pathway. To assess perforant pathway integrity in pure LBD we compared neuronal counts in layer II of the entorhinal cortex (ERC) in 11 cases of pure LBD that did not meet CERAD pathologic criteria for AD with ERC neuronal counts from seven AD cases with a similar disease duration and six cognitively normal individuals. We counted cell bodies/island in layer II of the ERC using formalin-fixed, paraffin-embedded, tau/cresyl violet-stained sections at the level of the rostral-most body of the hippocampus. There was marked variability in neuronal counts among cases in the LBD group; LBD data overlapped with data from both normal and AD groups. Overall, perforant pathway perikaryal counts in LBD differed significantly from those in AD, but not from those in aged normals (mean perikarya/island = 30.09 +/- 8.95, 7.57 +/- 6.08, and 38.83 +/- 8.98, respectively; F = 26.131, P < 0.001). The percent of remaining neurons bearing neurofibrillary tangles in LBD also overlapped with AD and control groups (16.17 = 13.85%, 87.86 +/- 11.81%, and 24.36 +/- 13.30% of remaining neurons, respectively, F = 65.62, P < 0.001). We conclude that although perforant pathway neuronal loss may occur in LBD, it is more often milder and more variable than that seen in AD.