Bone mass measurement at menopause to identify and selectively prescribe hormone replacement therapy for women at high risk for fractures has seen limited clinical use. We used epidemiologic, clinical, and economic data in a decision-analytic model to compare the following clinical strategies for perimenopausal, asymptomatic, white women with intact uteri: no intervention; bone mineral density measurement followed by selective, long-term (15-year) estrogen-progestin therapy in women with low bone mass; and unselective, universal hormone replacement therapy. Life expectancy and direct medical cost per patient were estimated for each strategy. Strategies for screening and treating women with perimenopausal bone mineral density < 0.9 g/cm2 or < 1.0 g/cm2 would cost $11 700 or $22 100, respectively, per year of additional life gained. If the cost of screening is less than $84, then resource savings from hip fractures prevented would be more than the cost of screening and treatment. Universal treatment without screening would prevent additional fatal fractures but would expose many more women to the adverse effects of hormone replacement therapy and would cost an additional $349 000 per year of life gained compared with the screening strategies. When quality of life was considered, screening was found to be cost effective over a wide range of assumptions. The choice between universal treatment and screening depends on the risks (breast cancer), perceived side effects (menstrual bleeding), and benefits (prevention of ischemic heart disease) of estrogen-progestin therapy. We conclude that screening asymptomatic, perimenopausal white women to detect low bone mass and to target hormone replacement therapy at women who are at the greatest risk for fracture is a reasonably cost-effective use of health care resources. However, cost-effective screening guidelines cannot be explicitly established until further data addressing the association between bone mass measurements in the hip and hip fracture risk are available.