Serum cholesterol binding reserve (SCBR) denotes the capacity of serum to solubilize additional cholesterol. It as been shown previously that a decrease of the SCBR in the presence of elevated cholesterol and/or triglyceride levels is associated with the development of coronary artery disease in man. This is a preliminary report of the effect on serum lipids and SCBR by alteration of the sex steroid environment in women. The hormonal changes associated with pregnancy appear to elevate cholesterol, triglycerides, and SCBR, SCBR being elevated to the greatest extent. No differences were observed in SCBR and serum lipids in a short-term study of premenopausal women when values prior to castration are compared with values after castration during administration of conjugated equine estrogens. In women observed over a period of over 20 weeks, who were using a combination oral contraceptive pill with 1 mg. of norethindrone and 50 or 80 mcg. of mestranol, there was a significant elevation of triglycerides, some decrease of cholesterol, and no change in the SCBR. The possible significance of these findings in relation to the risk of coronary heart disease deserves further investigation.