Prenatal diagnosis by first-trimester chorionic villus sampling was successful in 4319 pregnancies involving 4395 fetuses. Cytogenetic information was obtained by both rapid cytotrophoblastic preparation and monolayer mesenchymal tissue culture. Chromosomal mosaicism was present in 55 of 4319 (1.3%). The abnormal cell line involved the cytotrophoblast in 79.6% of the mosaic specimens. None of the abnormalities found in the cytotrophoblast were confirmed in the fetus when the tissue culture was normal, supporting the belief that the cells of the mesenchymal core more truly reflect the chromosomal constitution of the fetus. However, a significant increase in the perinatal loss rate in the placental mosaic group was noted when compared with the nonmosaics: 16.7 versus 2.7% (P = .0001). These findings suggest that placental mosaicism may be a cause of perinatal loss.