The putative precursor of A4 amyloid protein associated with Alzheimer's disease is known to have a domain with an amino acid sequence characteristic of a Kunitz-type serine protease inhibitor. Human serum inter-alpha-trypsin inhibitor (ITI) is the most similar inhibitor. We screened brain tissues with senile dementia of the Alzheimer type in an attempt to detect ITI immunoreactivity employing immunohistochemical methods. For this purpose, we used the antibody raised against acid-stable proteinase inhibitor (ASPI) which is an active component of ITI. ASPI immunoreactivity was found to be localized in diffuse type senile plaques, the perivascular area and subpial layer. Reactive astrocytes with intense ASPI immunoreactivity were present in the pyramidal layer of the parahippocampus, where loss of neurons was observed. These findings suggest that ITI may be related to the pathogenesis of Alzheimer type dementia.