The human supraoptic nucleus (SON) is the main production site of plasma vasopressin. Previously, using the Golgi apparatus and cell size as measures for neuronal metabolic activity, an activation of vasopressinergic neurons was found during ageing in the human SON in women but not in men. We hypothesized that the low-affinity neurotrophin receptor p75 (p75<sup>NTR</sup>) might be involved in the mechanism of activation of vasopressin neurons in postmenopausal women, since this receptor was found to be expressed in the SON neurons of aged individuals, and because p75<sup>NTR</sup> expression was shown to be suppressed by estrogens. Therefore, we investigated whether p75<sup>NTR</sup> immunoreactivity in the SON neurons was age- and sex-dependent. For this purpose, we studied paraffin sections of the SON in 32 postmortem brains of control patients ranging in age from 29 to 94 years with an anti-p75<sup>NTR</sup> antibody and determined the area of p75<sup>NTR</sup> immunoreactivity per neuron using an image analysis system. To study whether the p75<sup>NTR</sup> might also participate in the activation of SON neurons, we related Golgi apparatus size to the area of p75<sup>NTR</sup> immunoreactivity per cell in the same patients. We found that the area of p75<sup>NTR</sup> immunoreactivity per cell correlated indeed significantly with age and with Golgi apparatus size only in women but not in men. Therefore, our results suggest that p75<sup>NTR</sup> is involved in postmenopausal activation of vasopressinergic neurons in the human SON.