A role of estrogens in brain aging and Alzheimer's disease (AD) is a hot topic of research. We show in material of 71 patients that the estrogen receptor alpha (ERalpha) splice variant MB1 is expressed at the protein and mRNA level in the human brain. MB1 is mainly confined to astrocytes, membranes and cytoplasm of projecting neurons and endothelial cells. It was consistently observed in the thalamus, colliculus inferior, pontine nuclei, dorsal motor nucleus of vagus, some motor neurons in the anterior and lateral horns of the spinal cord and rarely in pyramidal neurons of the cerebral cortex. The highest level of MB1 immunoreactivity (MB1-ir) was noted in the caudal hypothalamus, in particular in the tuberomamillary nucleus (TMN). MB1-ir in the TMN increased during aging in women. MB1-ir was higher in young (<50 years of age) men than in premenopausal women. No significant changes of this variant were observed in the TMN of AD cases. In conclusion, MB1 may function as a dominant negative isoform in the human brain.