[125I]Apamin binding sites were examined using quantitative autoradiography in the hippocampus of 9 patients with Alzheimer's disease and 8 age-matched controls. Within the hippocampal formation from control subjects, [125I]apamin binding sites were highly concentrated in the subiculum and CA1. In Alzheimer's disease there was a marked and discrete loss of [125I]apamin binding sites in the subiculum (control = 1.10 +/- 0.10 pmol/g; Alzheimer = 0.71 +/- 0.09 pmol/g) and CA1 (control = 1.41 +/- 0.09 pmol/g; Alzheimer = 0.85 +/- 0.11 pmol/g; values are mean +/- S.E.M.). This reduction of [125I]apamin binding sites in the subiculum correlated with cell density but not neuritic plaque density. These results indicate that an anatomically discrete loss of Ca(2+)-dependent K+ channels within the hippocampal formation occurs in Alzheimer's disease.