To investigate whether factors influencing ovarian function affect risk of uterine leiomyomata, we examined prospectively the association of new diagnoses confirmed by ultrasound or hysterectomy with body mass index, weight change, height, and cigarette smoking among 94,095 premenopausal women with intact uteri, who were ages 25-42 years at the start of follow-up in 1989. We assessed body mass index and cigarette smoking from responses on the study questionnaire completed just before diagnosis. During 322,775 person-years, 2,967 new cases of uterine leiomyomata confirmed by ultrasound or hysterectomy were reported. Risk among all cases confirmed by ultrasound or hysterectomy increased with increasing adult body mass index. The multivariate relative risks (RR) and 95% confidence intervals (CI) according to body mass index categories of <20.0, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, 28.0-29.9, and > or =30.0 were 0.90 (95% CI = 0.79-1.03), 1.00 (referent), 1.08 (95% CI = 0.97-1.21), 1.16 (95% CI = 1.03-1.31), 1.21 (95% CI = 1.05-1.40), 1.36 (95% CI = 1.16-1.59), and 1.23 (95% CI = 1.09-1.39), respectively. The RRs for hysterectomy-confirmed cases generally were higher. Similarly, risk was positively associated with weight gain since age 18 years. Body mass index at age 18 years, height, and cigarette smoking were unrelated to risk of uterine leiomyomata. Elevated adult body mass index is associated with a modest increased risk of uterine leiomyomata among premenopausal women.