This study is the initial demonstration of trypsin-like immunoreactivity within the human CNS. Using two monoclonal antibodies to alpha 1-trypsin, we found trypsin-like immunoreactivity associated with the senile plaques of Alzheimer disease. Immunoblots prepared from homogenized Alzheimer and control cortex showed increased amounts of the 24,000Da alpha 1-trypsin species in diseased compared to control tissue. We suggest an alteration in alpha 1-trypsin protease regulation could be important in the formation of senile plaques and the pathogenesis of Alzheimer disease.