The authors conducted a case-control study among premenopausal women in the Baltimore, Maryland, area to examine the associations of uterine leiomyoma with ethnicity and hormone-related characteristics. Cases of uterine leiomyoma (n = 318) were surgically or sonographically first confirmed between January 1990 and June 1993. A total of 394 controls were selected from women who were visiting their gynecologist for a routine checkup. Data were collected through telephone interviews and abstraction of medical records; 77.8% of eligible cases and 78.0% of eligible controls were interviewed. Positive adjusted associations were observed between risk of uterine leiomyoma and self-described African-American ethnicity (vs. Whites: odds ratio (OR) = 9.4; 95% confidence interval (CI): 5.7, 15.7), early menarche (<11 years vs. >13 years: OR = 2.4; 95% CI: 1.1, 5.6), and high body mass index (upper quartile vs. lower quartile: OR = 2.3; 95% CI: 1.4, 3.8). Inverse associations were observed with use of oral contraceptives (current use vs. never use: OR = 0.2, 95% CI: 0.1, 0.6) and duration of smoking (> or =19 years vs. never: OR = 0.6; 95% CI: 0.4, 1.1). Younger ages at infertility diagnosis and at first and last childbirth were more common among cases; however, analyses of data on tumor location suggested that these associations represent predominantly consequences of uterine leiomyoma. These results suggest that development of uterine leiomyoma is associated with increased exposure to ovarian hormones. Possible reasons for the very elevated risk among African-American women need further investigation.