Background: Hyperlipidemia and its related complications are among the most frequent problems during the menopause. Controversies have arisen regarding the effects of hormone replacement therapy on serum lipids during the menopause, so the present study was conducted over the menopausal women referring to the hospitals of Shaheed Beheshti University of Medical Sciences in 1998-99.Materials and methods: 40 menopausal females ahd entered this clinical trial. Including criteria were: non-obesity (BMI<30), normal uterus, blood pressure<160/90mnHg, no previous history of diabetes, hypothyroidism, renal failure, acute liver disease, and breast cancer. Meanwhile, candidates should have no obligation for estrogen-therapy (such as thrombophlebitis, ...). 8cc blood sample was obtained for FSH, FBS, LFT, triglyceride, cholesterol, HDL, and LDL measurement. FSH was measured through radioimmunoassay and lipid parameters were determined enzymatically. Hormone replacement therapy was administered for 3 months as below: conjugated estrogen 0.625mg/d, first to 25th day of each menstrual cycle as well as medroxyprogestrone acetate 10mg/d, 15thto 25th day of each menstrual cycle. Then, blood samples were obtained and lipidemic parameters were determined and compared with the previous results.Results: The mean age (±SD) of the candidates was 53.9±2.83 and the mean age of menopausal was 51.9±1.45 years. Serum cholesterol level was reported 197.4±37.9 mg/dl before the hormone replacement therapy, but was decreased by 17% (162.4±31.5mg/dl) after that (p<0.001). However, HDL level has shown 14.91% increase after the therapy (50.3±12.2 vs. 57.8±14.5 mg/dl). Meanwhile, LDL and triglyceride levels have shown 21.4% and 9.56% reduction following the procedure (124.5±44.5 vs. 97.8±34.3 mg/dl, and 163.4±55.98 vs. 147.7±52.47 mg/dl, respectively, p<0.001).Conclusion: Hormone replacement therapy could reduce serum lipid level in menopausal females. Another study regarding the efficacy of hormone replacement therapy on hyperlipidemic menopausal females is strongly recommended.