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Neuroleptic hypersensitivity is characteristic of dementia with Lewy bodies (DLB) but not of other dementias. The authors report 5 patients with psychotic mood disorders and long-standing antipsychotic drug therapy. As they reached 50 to 60 years of age, they unexpectedly developed hypersensitivity to these medications, with rigidity, muteness, or the neuroleptic malignant syndrome. Nearly coincident with this reaction, they developed progressive cognitive deficits consistent with frontotemporal dementia. These patients illustrate emergent neuroleptic hypersensitivity as an early manifestation of other dementias. The predisposition to neuroleptic hypersensitivity could result from depleted nigral dopaminergic neurons suggested by “smudging” of the substantia nigra pars compacta on magnetic resonance imaging.