The neurotoxic beta-amyloid peptide of Alzheimer's disease is formed from the amyloid precursor protein (APP), which is a member of an evolutionarily highly conserved gene family with significant functional importance. Because behavioral and psychiatric symptoms treated with antipsychotics may influence the course of the disease, we have investigated traditional and atypical antipsychotic drugs, administered through the intraperitoneal route, for their effects on rat cortical APP. Western-immunoblotting was utilized for semi-quantitative evaluation of APP levels. Treatment with haloperidol resulted in an acute elevation of cortical APP both in therapeutic and toxic doses, however, it had no significant chronic impact on APP. Atypical antipsychotic risperidone did not change cortical APP concentration. These results indicate that both haloperidol and risperidone are considered to be relatively safe with respect to APP metabolism. Possible mechanisms, including involvement of calcium and APP itself as a receptor, are discussed.