Neuronal hypertrophy occurs in a subpopulation of neurons in the infundibular nucleus of post-menopausal women. The hypertrophied neurons contain NKB, SP and estrogen receptor gene transcripts. Although associated with reproductive aging, post-menopausal neuronal hypertrophy is not a sign of central nervous system degeneration. Quite the opposite, because the hypertrophy is accompanied by marked increases in tachykinin gene expression, reflecting increased neuronal activity. We have proposed that infundibular neurons containing NKB, SP and estrogen receptor mRNAs participate in the hypothalamic circuitry regulating estrogen negative feedback on gonadotropin release in the human. In addition, there is evidence to suggest that the hypertrophied tachykinin neurons may be involved in the initiation of menopausal flushes. Because menopause affects a well characterized system, and has consistent and substantial changes in hormone levels, we have had the rare opportunity to correlate changes in hormone secretion with structural and neurochemical changes in the human hypothalamus. We suspect that future studies of the hypothalami of post-menopausal women will continue to be a fruitful avenue for investigating neuroendocrine regulation in the human.