Uterine leiomyomata are hormonally dependent tumors that are a major source of gynecologic morbidity among women of reproductive age. Relatively few studies have attempted to identify specific risk factors for these neoplasms. In this review of epidemiologic contributions to the etiology of uterine leiomyomata, we begin by outlining methodologic issues in epidemiologic studies that arise from the fact that a large proportion of uterine leiomyomata does not come to medical attention. We then review the major findings from published epidemiologic studies, which to date have focused primarily on menstrual and childbearing history, exogenous hormone use, obesity, cigarette smoking, and other lifestyle and behavioral characteristics that may in part reflect aspects of a woman's hormonal milieu. None of the potential risk factors studied have demonstrated sufficiently consistent associations to guide decisions on the primary prevention of uterine leiomyomata. Clarifying the etiology and natural history of uterine leiomyomata will require studies designed to address methodologic issues and test hypotheses involving environmental and lifestyle influences on endocrine function, as well as on other possible etiologic mechanisms. Recent advances in molecular genetics present opportunities for epidemiologic studies of uterine leiomyomata to incorporate biomarkers of somatic changes found in these tumors and to examine inherited genetic factors related to possible causal physiologic mechanisms.