We performed immunocytochemistry to localize alpha 1-antichymotrypsin and alpha 1-antitrypsin in tissue sections of Alzheimer disease patients. Our results show that both serine protease inhibitors are localized in neurofibrillary tangles and senile plaques. Using various monoclonal and polyclonal antibodies, immunolabeling was evident in formalin, methacarn or acetone-fixed sections. Brief pretreatments of sections with either formic acid or guanidine-HCl were also necessary to reveal clear immunostaining of the lesions with two of the antibodies. We suggest that both alpha 1-antitrypsin and alpha 1-antichymotrypsin may be functionally involved in the pathogenesis of the lesions of Alzheimer's disease. Like alpha 1-antichymotrypsin, the major cell producing alpha 1-antitrypsin is likely to be astrocytes since the protein was localized there and astrocytes are involved in both lesions.