We assessed muscarinic M(1), M(2) and M(4) receptor subtypes in the hippocampus of Alzheimer's and control brains by receptor autoradiography using ligands such as [(125)I]muscarinic toxin-1 ([(125)I]MT-1, M(1) selective), [(3)H]AFDX-384 (M(2) partially selective) and [(125)I]muscarinic toxin 4 ([(125)I]M(4) toxin-1, M(4) selective). Our results revealed a significant decrease in muscarinic M(4) receptor binding in the dentate gyrus and CA4 regions of brain sections from Alzheimer's patients compared to controls. No changes in the density of M(1) or M(2) receptor binding were observed. Our findings suggest that, relative to other muscarinic receptor subtypes, the M(4) receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD).