Objective: This study was undertaken to evaluate the efficacy and safety of closing the fetoscopy access site in a midgestational rabbit model by using a commercially available bioactive membrane. Study Design: Fetoscopy was performed in a total of 100 gestational sacs in 20 does at midgestation (23 days, term = 31 days). In 50 cases (group 1), the fetoscopic access port was closed with a 5-mm patch of biocompatible matrix derived from porcine small intestine containing growth factors (transforming growth factor-β and fibroblast growth factor-β). Fifty sacs served as positive controls (group 2) and 55 unoperated fetuses were used as negative controls (group 3). At 30 days of gestation, a second-look laparotomy was performed. Outcome parameters were fetal weight, fetal lung weight, fetal lung-to-body weight ratio, and microscopy of the plugging site. Results: Membrane integrity after fetoscopy was restored in 28 of the 40 (70%) of cases in group 1 versus 13 of the 32 (41%) in group 2 (P =.012). Birth weights were comparable (group 1: 30.65 ± 5.68 g; group 2: 29.70 ± 5.05 g; group 3: 29.52 ± 6.25 g; NS), but fetal lung weight (group 1: 0.964 ± 0.20 g; group 2: 0.798 ± 0.17 g; P <.01) and fetal lung-to-body weight ratio (group 1: 0.032 ± 0.0067; group 2: 0.027 ± 0.0082; P <.05) were significantly higher in the study group. In group 1, cellular proliferation was significantly increased. Polymorphonuclear infiltration was observed in 19 of the 40 (48%) cases in group 1 versus 5 of the 32 (16%) cases in group 2 (P <.05). In one treated sac, a fibrous band joining the two fetal legs without constriction was present. Conclusion: The use of a bioactive membrane improved fetal membrane repair rates and decreased incidence of pulmonary hypoplasia in the rabbit but increased polymorphonuclear infiltration. In one amniotic sac, a situation comparable to amniotic band syndrome was documented. (Am J Obstet Gynecol 2003;188:844-8.)