To learn about the carboxy-terminal extent of amyloid g-protein (Ag) composition of senile plaques (SPs) in the brain affected with Alzheimer’s disease (AD), we employed two end-specific monoclonal antibodies as immunocytochemical probes: one is specific for Ag40, the carboxyl terminus of Agl-40, while the other is specific for Ag42 (43). In the AD cortex, all SPs that were labeled with an authentic antibody were Ag42 (43) positive, while only one-third of which, on the average, were Ag40 positive. There was a strong correlation between Ag40 positivity and mature plaques. Two familial AD cortices with the mutation of g-amyloid protein precursor 717 (gAPP717)(val to Ile) showed a remarkable predominance of Ag42 (43)-positive, Ag40-negative plaques. Diffuse plaques, representing the earliest stage of Ag deposition, were exclusively positive for Ag42 (43), but completely negative for Ag40.