Objective: As pelvic organ prolapse progresses, the morphology of the vagina dramatically changes. The objective of this study was to determine whether these changes observed clinically correlate with histologic and biochemical evidence of tissue remodeling. METHODS: After informed consent, fullthickness biopsies of the vaginal apex were obtained at the time of surgery from 77 women. The tissue of 15 premenopausal women with less than stage II prolapse (controls)was compared with that of 62 women with prolapse divided according to their menopausal status. All specimens were examined histologically. Scanning confocal microscopic analysis of fluorescent micrographs was used to quantitate collagen subtypes I, III, and V. Collagen fiber orientation was analyzed by scanning electron microscopy. Gelatin zymography was used to quantitate the expression of the proenzyme and active forms of matrix metalloproteinases (MMP)-2 and-9. Median values were compared using Mann-Whitney U or Kruskal- Wallis tests, where appropriate. RESULTS: Vaginal collagen fibers are arranged in a whorled pattern, with collagen III as the predominant fibrillar collagen. The amount of total collagen in the vagina was increased in women with prolapse relative to women without prolapse (P = .054) primarily due to increased expression of collagen Ⅲ(P = .031). There was no difference in the expression of proMMP-2, active MMP-2, or proMMP-9; however, active MMP-9 was increased in patients with prolapse (P = .030). CONCLUSION: The increase in collagen III and active MMP-9 expression in the vaginal tissues of patients with prolapse suggests that this tissue is actively remodeling under the biomechanical stresses associated with prolapse. Objective: As the pelvic organ prolapse progresses, the morphology of the vagina dramatically changes. The objective of this study was to determine whether these changes observed clinically correlate with histologic and biochemical evidence of tissue remodeling. METHODS: After informed consent, fullthickness biopsies of the vaginal apex were obtained at the time of surgery from 77 women. The tissue of 15 premenopausal women with less than stage II prolapse (controls) was compared with that of 62 women with prolapse divided according to their menopausal status. All specimens were examined histologically. Scanning confocal microscopic analysis of fluorescent micrographs was used to quantitate the collagen subtypes I, III, and V. Collagen fiber orientation was analyzed by scanning electron microscopy. Gelatin zymography was used to quantitate the expression of the proenzyme and active forms of matrix metalloproteinases (MMPs) 2 and-9. Median values ​​were compared using Mann-Whitney U or Kruskal-Wal lis tests, where appropriate. RESULTS: Vaginal collagen fibers are arranged in a whorled pattern, with collagen III as the predominant fibrillar collagen. The amount of total collagen in the vagina was increased in women with prolapse relative to women without prolapse (P =. There was no difference in the expression of proMMP-2, active MMP-2, or pro MMP-9; however, active MMP-9 was increased in patients with prolapse (P = .030). CONCLUSION: The increase in collagen III and active MMP-9 expression in the vaginal tissues of patients with prolapse suggests that this tissue is actively remodeling under the biomechanical stresses associated with prolapse.