Objective: To study the correlations between estrogen receptor (ER) and androgen receptor (AR) and the clinical presentations of prolactinoma and investigate the effect of ER and AR expression on the pathogenesis of prolactinoma in sexual difference. Methods: The clinical data of 30 patients who had undergone transsphenoidal operations in Tongji Hospital from December 2000 to December 2001 were reviewed retrospectively. The clinical information included sex, age, serum-prolactin, size, tumor invasiveness, history of use of bromocriptine and frequency of recurrence. In 20 out of the 30 patients, the ER and AR expression was detected by using immunohistochemistry method. With help of Chi-square test, the relationship between ER, AR and the clinical presentations was analyzed. Results: The statistical values revealed that there was no significant correlation between the ER and AR expression levels with the clinical presentations such as sex, age, tumor size or tumor invasiveness among the 20 patients studied (P >0.05). Conclusion: The expression of ER or AR is not influenced by the clinical data of prolactinoma such as sex, age, tumor diameter or extent of tumor invasiveness. The tumor is more aggressive in males than in females. In maroadenoma or tumor with hyperprolactineamia (>200 ng/mL) simple surgical treatment can't successfully cure the prolactinoma. Post-operative bromocriptine therapy can't be determined by the sex of the patients, but is greatly related to the tumor size and serum-prolactin level before operation.Several theories explaining the pathogenesis of prolactinoma have been suggested according to the different sub-branches of neurosurgery such as onco-neurosurgery, radio-neurosurgery, neuro-endocrinology etc. De Nicola and Wicklan et al had successfully induced an animal model of prolactinoma tumor in their experimental studies in F-344 male and female rats by giving them estrogen [1] .The physiological effects of estrogen on pituitary including cell proliferation and regulation in hormone synthesis are mediated by the estrogen receptor (ER) [2,3] .Brain-especially the hypothalamus contains aromatase enzyme, which is responsible for the formation (aromatization) of estrogen from androgen in situ.In this study, the effects of estrogen and androgen were investigated through analyzing the expression of their respective nuclear receptor in the prolactinoma tissues in order to find out the correlation between ER and androgen receptor (AR) and the clinical characteristics of prolactinoma.