The human nucleus basalis of Meynert (NBM) is severely affected in Alzheimer's disease (AD). Since estrogens may reduce both the risk and severity of AD, possibly by an action on the cholinergic system, we determined whether estrogen receptors are present in the human NBM and what their changes are in normal aging and in AD. ERalpha was expressed to a higher degree than ERbeta and was localized mainly in the cell nucleus, while ERbeta was mainly confined to the cytoplasm. A significant positive correlation between the percentage of ERalpha nuclear positive neurons and age was found in men but not in women, whereas the proportion of ERbeta cytoplasm positive cells increased during aging in both sexes. In AD the proportion of neurons showing nuclear staining for both ERalpha and beta and cytoplasmic staining for ERbeta was markedly increased. The percentage of ERbeta nuclear positive neurons increased in AD only in women but not in men. The ApoE genotype had no effect on ER expression in the NBM in AD. In conclusion, whereas only minor sex- and age-related changes in both ERs were found in the human NBM, a clear upregulation of ERalpha and beta was observed in AD.