In a longitudinal prospective study of dementias, several hundred cases have been examined from a clinical, brain imaging, neurochemical and neuropathological point of view. Frontal lobe degeneration of non-Alzheimer type (FLD) was the second most common primary degenerative dementia found in about 10% of the material. FLD has a consistent pathology and a characteristic clinical picture, which have been described by several independent research groups. The cortical degeneration mainly involves frontal or frontotemporal grey matter, without the circumscribed or knife-blade atrophy seen in Pick's disease. The degeneration involves predominantly frontal areas, including the insula and cingulate gyrus in its anterior parts. The striate body is normal or only slightly altered. The pathological changes are non-specific, with neuronal loss, slight gliosis and spongiosis but none or few senile plaques, tangles, congophilic vessels or Pick cells. Pathological changes are in some respects similar to those in amyotrophic lateral sclerosis. FLD is a slowly progressive dementia with personality changes, lack of insight, disinhibition, stereotypy and later apathy. There is also progressive dynamic aphasia which ends in mutism and amimia. Memory, spatial ability and receptive language functions are comparatively spared. Psychotic symptoms, emotional reactions, hypochondriasis and a Klüver-Bucy-like syndrome are sometimes observed. Electroencephalography is normal, at least during the early stage, while functional brain imaging such as regional cerebral blood flow reflects the frontal pathology. It is possible to achieve early diagnosis and differentiation from Alzheimer's disease and cerebrovascular dementia by clinical examination with neuropsychological assessment supported by brain imaging, and in the future probably various biological markers. The aetiology is unknown but there is a positive family history for dementia of similar type in about 50% of post-mortem verified cases.