The pineal secretory product melatonin has, in addition to regulating retinal, circadian and vascular functions, neuroprotective effects. Blood melatonin levels are often decreased in Alzheimer's disease (AD), a progressively disabling neurodegenerative disorder. In this study we provide the first immunohistochemical evidence for the localization of melatonin 1a-receptor (MT(1)) in aged human hippocampus and a comparison of AD cases. MT(1) was localized to pyramidal neurons in the hippocampal cornu ammonis (CA)1-4 subfields. There was a distinct increase in staining intensity in all AD cases indicating an up-regulation of the receptor, possibly as a compensatory response to impaired melatonin levels in order to augment melatonin's neuroprotective effects.