Although uterine leiomyomas are a major public health problem, very little is known about their etiology or histogenesis. To seek clues as to why the myometrium so frequently gives rise to these tumors, we attempted to determine if the regional distribution of leiomyomas was uniform. It appears that the proportion of leiomyomas in the premenopausal (0.8%) and postmenopausal (3.7%) cervix may be substantially less than the proportion of smooth muscle in the premenopausal (7.3%) and postmenopausal (17%) cervix. These data suggest that the smooth muscle cells of the corpus uteri may be at higher risk for neoplastic transformation than those of the cervix. Within the corpus there appeared to be a relative excess of fundic leiomyomas (premenopausal, 89%; postmenopausal, 86%) as compared with fundic smooth muscle (premenopausal, 79%; postmenopausal, 61%). No such excess was apparent in the isthmus or cornu. Immunohistochemical studies of estrogen and progesterone receptors in premenopausal and postmenopausal myometrium were uniformly positive, with no regional differences to suggest a hormonal basis for regional susceptibility to leiomyomas. It may be fruitful to search for precursor lesions and other factors predisposing to neoplastic development in fundic myometrium.