OBJECTIVE: To explore a possible association between estrogen receptor-alpha (ER-alpha) gene polymorphisms and development of uterine leiomyomas. DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): 119 women with clinically and surgically diagnosed uterine leiomyomas. INTERVENTION(S): Therapeutic hysterectomy. MAIN OUTCOME MEASURE(S): Frequency and distribution of ER-alpha gene polymorphisms. RESULT(S): No statistically significant differences between controls and patients in the allele frequency and genotype distribution were found when Pvu II and Xba I restriction polymorphism sites were analyzed separately. When the two ER-alpha gene polymorphisms were analyzed in combination, five major genotypes were recognized in controls or patients; the frequency differed slightly but not significantly between groups. CONCLUSION(S): The Pvu II and Xba I polymorphisms in the ER-alpha gene do not produce different risks of developing uterine leiomyomas.