The authors report a new kindred with fatal familial insomnia (FFI)--an inherited prion disease. The propositus had behavioral, sleep, cognitive, and motor impairment associated with thalamic and olivary atrophy. Spongiosis was confined to the parahippocampal gyrus. Protease-resistant prion protein (PrP(res)) was present with widespread distribution. The propositus fits the histopathology of FFI with similar clinical duration and confirms the role of disease duration in determining histopathology and PrP(res) distribution in FFI.