Premature ovarian failure (POF) and Turner's syndrome patients who are also hypoestrogenomic, like postmenopausal women, are considered to be a high risk group for hyperlipemia. Our long-term study was conducted to evaluate the effect of hormone replacement therapy (HRT) on lipid metabolism in 16 POF and 10 Turner's syndrome women. 1. The initial average total cholesterol (TC) of the untreated and treated POF patients (209, 196mg/dl) and that of untreated and treated Turner's syndrome patients (213, 240mg/dl) were significantly higher than those in the control group (175mg/dl) except treated POF patients. LDL cholesterol (LDL-C) of the untreated and treated POF patients (135, 113mg/dl) and that of untreated and treated Turner's syndrome patients (142, 144mg/dl) were significantly higher than those in the control group (108mg/dl) except treated POF patients. In comparison to healthy women of a similar age, POF and Turner's syndrome patients were at high risk of hyperlipemia because of higher serum TC and LDL-C levels. 2. After HRT for 2 years, LDL-C decreased by 18% and 13%, and HDL cholesterol increased by 38% and 41% in POF and Turner's syndrome patients, respectively. Hence AI decreased by 40% and 50% respectively. The younger the hyperlipemic patients are, the higher the relative risk for atherosclerosis is. The results of this study suggest that, because of the beneficial effects of HRT on serum lipid metabolism, it can help to prevent the development of coronary heart disease.