OBJECTIVE: Our purpose was to determine whether maternal parity affects analyte levels in the multiple-marker screening test for Down syndrome and to derive a correction factor and determine its effect on Down syndrome detection and screen-positive rates. STUDY DESIGN: Our database consisted of 3039 multiple-marker screening test results and corresponding fetal karyotypes (2983 euploid and 56 Down syndrome). Cases were grouped by maternal parity as follows: 0 (n = 848), 1 (n = 1140), or ≤2 (n = 1051). The mean multiple of the median of maternal serum α-fetoprotein, estriol, and human chorionic gonadotropin was determined for each group. A correction factor was derived for each parity group and applied to the database. Parity- corrected Down syndrome detection rates and screen-positive rates were determined. RESULTS: Parity significantly affected the mean multiple of the median of human chorionic gonadotropin levels (p = 0.0001) but did not affect the values for estriol or maternal serum α-fetoprotein. Application of a parity correction factor for human chorionic gonadotropin increased the Down syndrome detection rate in women who had two or more pregnancies from 71% to 82% without increasing the overall screen-positive rate. CONCLUSION: Human chorionic gonadotropin levels are significantly lower in multiparous women. Correcting human chorionic gonadotropin for maternal parity increases Down syndrome detection for women who had two or more pregnancies without affecting the overall screen-positive rate.