OBJECTIVE: The endothelin-1 system regulates (myo)fibroblast contraction in wound healing. Our aim was to determine endothelin-1 system expression and function in contractile properties of vaginal myofibroblasts of women with uterovaginal prolapse. STUDY DESIGN: Cultures of alpha-smooth muscle actin-positive myofibroblasts that were established at the time of repair surgery for prolapse (n = 30; mean age, 56 +/- 14 years) were analyzed and compared for their expression of the endothelin-1 system and contractile properties to myofibroblasts from primiparous women. RESULTS: Myofibroblasts expressed the complete endothelin system but did not secrete endothelin-1. Endothelin-1 binding was mediated exclusively by the endothelin B-receptor. In 3-dimensional collagen gels, spontaneous contraction of myofibroblasts from estrogen-treated women with prolapse was statistically significantly lower than from young primiparous women. Exogenous addition of endothelin-1 decreased the spontaneous contraction of myofibroblasts. CONCLUSION: Genital myofibroblasts of women with uterovaginal prolapse are poorly contractile, and endothelin-1 further decreases vaginal myofibroblast contraction, which is opposite to observations in skin myofibroblasts.