The monoclonal antibody Alz-50 is directed against modified forms of tau proteins. Various hypotheses have been put forward concerning the meaning of Alz-50 staining in Alzheimer's disease brains. Cytoskeletal alterations are reported to occur exclusively in the cortex and the subcortical nuclei directly connected with the cortex. In addition, Alz-50 staining is presumed to be indicative of impending neuronal death. In order to test these hypotheses Alz-50 was applied to the hypothalamus and adjoining areas of five Alzheimer's disease patients of 40-90 years of age and five sex- and age-matched, non-demented controls. The results showed the following: (i) Alz-50 immunoreactivity is not restricted to Alzheimer's disease patients. Alz-50 immunoreactive beaded nerve fibres and patchy, granular cell bodies were observed in some hypothalamic nuclei of all controls with the exception of the youngest one. Dystrophic neurites were not only observed in all Alzheimer's disease hypothalami but also in that of the oldest control. (ii) In the hypothalamic area various nuclei had different Alz-50 staining patterns. Alz-50 staining could not, however, be related to neuronal death in the different nuclei. (iii) Histopathological changes in Alzheimer's disease patients are not restricted to the cortex or subcortical areas connected directly with the cortex. The present report indicates that the hypothalamus is considerably more affected in Alzheimer's disease than has often been assumed. However, these changes can also be found in non-demented old people.