Hot flushes are not caused by hypergonadotrophinaemia. This is apparent because peaks of gonadotrophin in the serum do not coincide with cutaneously measured hot flushes while such flushes still occur in hypophysectomized women. Gonadotrophin-releasing hormone and other neurotransmitters (possibly beta-endorphin) affect thermoregulation. The following hypothesis is advanced. During the climacteric period neurotransmitter changes, a decrease in catechol oestrogens, a decrease in alpha-2-adrenoceptor activity and cessation of ovarian steroid production may lead to alterations in endogenous opiate activity and thus to disturbances of thermoregulation, resulting in the occurrence of hot flushes. Low beta-endorphin levels in the peripheral plasma, which rise again following oestrogen treatment, are observed during the climacteric. On the other hand, women with severe hot flushes caused by a stress event show enormously increased beta-endorphin values, which are normalized by hormone substitution therapy acting via still unknown neuroendocrinological feedback mechanisms.