Objective: Measurement of cell- free fetal (cff) DNA in maternal plasma may have clinical application in prenatal screening for fetal Down syndrome and preeclampsia. Little is known regarding the tissue of origin of these fetal-derived sequences. We tested the hypothesis that if the placenta is the major contributor of cff DNA, then an increased placental volume should be associated with higher maternal plasma cff DNA levels. Study design: We enrolled 143 pregnant women who underwent first trimester placental volume measurement using 3- dimensional ultrasonography. Cff DNA in maternal plasma on the day of the scan was quantified by real-time polymerase chain reaction (PCR) amplification of a Y- chromosome sequence. The association between measured placental volume and maternal plasma cff DNA levels was analyzed along with relevant clinical variables. Results: The median (25th, 75th percentiles) maternal plasma cff DNA level was 16.9 genome equivalents (GE)/mL (10.8, 28.7). Raw values were adjusted for gestational age and maternal body mass index. Results: The median (25th, 75th percentiles) placental volume was 53.2 mL (43.0, 64.7), and median placental quotient (ratio of placental volume to fetal crown-rump length) was 1 mm2 (0.8, 1.1). Based on multivariate linear regression analyses, neither of the above placental measurements showed a significant association with maternal plasma cff DNA levels (P = .43 and .43, respectively). A modest association was found between plasma cff DNA levels and gravidity (P = .03). Conclusion: Our data did not show a significant association between either the placental volume or placental quotient, and maternal plasma cff DNA levels. We speculate that it is the extent of placental apoptosis that primarily affects the amount of cff DNA released into the maternal circulation. Objective: Measurement of cell-free fetal (cff) DNA in maternal plasma may have clinical application in prenatal screening for fetal Down syndrome and preeclampsia. Little is known regarding the tissue of origin of these fetal-derived sequences. We tested the hypothesis that if the design of We enrolled 143 pregnant women who underwent first trimester placental volume measurement using 3- dimensional ultrasonography. Cff DNA in maternal plasma on the day of the scan was quantified by real-time polymerase chain reaction (PCR) amplification of a Y-chromosome sequence. The association between measured placental volume and maternal plasma cff DNA levels was analyzed along with relevant clinical variables. The median (25th, 75th percentiles) maternal plasma cff DNA level was 16.9 genome equivalents (GE) / mL (10.8, 28.7). Raw values ​​w Results: The median (25th, 75th percentiles) placental volume was 53.2 mL (43.0, 64.7), and median placental quotient (ratio of placental volume to fetal crown-rump length) was 1 mm2 (0.8, 1.1). Based on multivariate linear regression analyzes, neither of the above placental measurements showed a significant association with maternal plasma cff DNA levels (P = .43 and .43, respectively). A modest association was found between plasma cff DNA levels and gravidity (P = .03). Conclusion: Our data did not show a significant association between either the the placental volume or placental quotient, and maternal plasma cff DNA levels. We speculate that it is the extent of placental the amount of cff DNA released into the maternal circulation.