To study the possible association between transcervical chorionic villus sampling and midtrimester oligohydramnios, we conducted a prospective cohort study of all women who were seen for genetic counseling in the first trimester during a 2-year period. Women who chose chorionic villus sampling were compared with women who chose traditional amniocentesis for incidence of midtrimester oligohydramnios. Of 442 women exposed to chorionic villus sampling with a normal fetal karyotype, severe oligohydramnios developed in 12 (2.7%) at 16 to 23 weeks' gestation. None of the 391 women with normal fetal karyotypes who were counseled at the same time in pregnancy but who chose amniocentesis had oligohydramnios at the time of amniocentesis (p = 0.01). A nested case-control analysis was performed within the chorionic villus sampling group to evaluate risk factors associated with midtrimester oligohydramnios. Midtrimester oligohydramnios occurring after chorionic villus sampling was associated with postprocedure bleeding and elevated maternal serum alpha-fetoprotein (p less than 0.01). There were no perinatal survivors with midtrimester oligohydramnios.