Endothelin (ET) and its mRNA are present in human endometrium. Its expression varies across the menstrual cycle, reaching maximal levels in the pre-menstrual phase. Human endometrial epithelial cells are the major in-vitro source of ET, and its release is affected by the stage of the menstrual cycle from which the endometrium is taken and by the cytokines transforming growth factor-beta 1 and interleukin-1 alpha. The cyclical variation in both ET mRNA and protein expression across the normal menstrual cycle, and the differences observed in abnormal uterine bleeding (specifically reduced immuno-reactivity in luminal and glandular epithelium in the endometrium of Norplant users), are consistent with a role for ET in the control of menstrual bleeding. The role of epithelial cell ET is not yet understood. Whether this source of ET is important in endometrial regeneration and repair following menstruation or in vaso-constriction to cease menstrual bleeding remains to be determined.