Objectives: To assess the endometrial contribution of serum CA125 and its influence from estrogen administration in menopausal women. Design: A randomised, controlled, prospective study. Materials and Methods. Twenty menopausal women with intact uterus and ovaries (study group) and ten cases with total hysterectomy were selected through a random table among the referred menopause patients for hormone replacement therapy. Mean ages and menopause lengths of the study and control groups were similar. Ten cases and five controls had 15 days of transdermal 100 μm/d estradiol (TE) (group 2), and similarly the other cases with five controls had estradiol were measured at day same period of time (group 1). Serum CA125 and estradiol were measured at day 0 and by radio immunoassay (RIA). Statistics were analysed by paired and unpaired Student's test where appropriate. Results: Serum mean CA125 levels increased in endometrium intact menopausal women from day 0 to 15 of TE administration in group 2 and 1, 70% and 6% respectively (p=0.03 and 0.05). Serum estradiol accompanied this increase only in group 2 significantly. Conclusion: Endometrial CA125 secretion to serum is dependent on the dose of exogenous estrogen administered. Th subject population used in this study is a good model to assess the endometrial contribution of serum CA125 with exogenous estrogen administration by ruling out ovarian activity.