The age-related morphological changes in the darkly stained sex-dimorphic nucleus (SDN-POA) and the lighter staining surrounding area (non-SDN-POA) within the medial division of preoptic nucleus of Long-Evans rats were studied. The long-term effects of estradiol benzoate (EB) on the changes were also assessed. During aging, the neuron loss in 14-(middle-age) and 22-month-old rats as well as increased pyknotic ratio of neurons in old male rats were observed in SDN-POA, but not in the non-SDN-POA. In female rats, significant neuron loss with advancing age was observed both in SDN-POA and the non-SDN-POA. Neuron loss in SDN-POA of EB-treated males was more severe than that of the intact males, while no significant difference of neuron loss was observed between EB-treated and age-matched intact female rats. However, neuron loss in SDN-POA of ovariectomized female rats was more severe than that of the age-matched intact females. These results indicate that age-related neuron loss in medial preoptic nucleus show sex-specific and area-specific features, and estradiol may play a important role in modulating neuron loss during aging.