WE studied neuronal alterations in the Lewy body variant of Alzheimer's disease (LBV) with a monoclonal antibody (SMI32) against non-phosphorylated neurofilament proteins, and compared them with the alterations found in pure Alzheimer's disease (AD). A characteristic granular and fragmented appearance of SMI32-immunolabeled pyramidal neurons in layers 3 and 5 of the neocortex occurred in 78% of the LBV cases and was not found in the pure AD cases. Lewy bodies (LBs) in pyramidal neurons in layers 5 and 6 immunoreacted with SMI32 in 44% of the LBV cases. These alterations may be associated with the cognitive deficits found in LBV and are suggestive of an underlying, widespread pathology that includes both disruption of the neurofilamentous cytoskeleton and formation of LBs.