Background: Uterine fibroids represent the leading indication for roughly 600,000 hysterectomies performed annually in the United States. There is no satisfactory long-term medical therapy for fibroids, which disproportionately affect black women. Preliminary data from our open label study show that oral administration of mifepristone 5 mg per day is associated with significant improvement in fibroid symptoms and nearly 50% reduction in fibroid size. However, findings from this study were limited by absence of a placebo control group, absence of blinding, and absence of a validated, disease-specific quality of life outcome measure. Aims: We propose a six-month randomized, double-blinded, placebo-controlled trial of low-dose mifepristone. Seventy women with moderate to severely symptomatic fibroids, confirmed by ultrasonography, will be randomly allocated to receive mifepristone 5 mg per day or an identical appearing placebo. The primary outcome measure will be change in disease-specific quality of life based on the recently validated Uterine Fibroid Symptom Quality of Life questionnaire. Secondary outcomes include change in global health status, fibroid size, pain, bleeding, and adverse effects including endometrial hyperplasia. We also propose to test the hypothesis that administration of mifepristone will be associated with significant reductions in fibroid blood flow, which in turn, will be associated with reductions in fibroid volume. Significance: The study offers the promise for a safe, effective medical treatment for symptomatic fibroids that could potentially benefit millions of women world-wide, prevent thousands of hysterectomies and reduce health care costs. The study may also offer valuable insight into a mechanism by which mifepristone reduces fibroid size.