Objectives: The aim of the study was to determine whether the pregnant rabbit at mid gestation could be used as a suitable in vivo model for the study of membrane defects after invasive procedures. Study Design: Pregnant rabbits at gestational ages of 22 and 18 days (term is 32 days’ gestation) underwent needle insertion with different instrument diameters (1.1 mm, 1.35 mm, 2.0 mm, and 2.7 mm). Two different insertion techniques were evaluated, blind amniotic puncture and puncture through surgically exposed amnion. Membrane integrity, presence of amniotic fluid, and fetal lung/body weight ratio were evaluated at 31 days’ gestation. Results: Among rabbits operated on at 22 days’ gestation the amniotic integrity restoration at 31 days’ gestation ranged from 46% to 76% in the different diameter and access technique groups, as compared with 98% in untreated sacs (P < .05 for all groups). Fetuses from sacs with persisting membrane defects had oligohydramnios and significantly lower fetal lung/body weight ratios. Survival rates among fetuses operated on at 18 days’ gestation were so poor that appropriate statistical analysis was not possible in this group. Conclusions: The rabbit at mid gestation can be used as a model to reproduce permanent membrane defects after fetoscopy, reproducing oligohydramnios and pulmonary hypoplasia. This may provide a suitable in vivo model for the study of iatrogenic membrane defects. (Am J Obstet Gynecol 1999;180:1263-7.)