OBJECTIVE: Our purpose was to determine the effect of maternal weight on human chorionic gonadotropin concentration in the multiple-marker screening test for fetal Down syndrome. STUDY DESIGN: Two genetics databases were used: database I contained the results of 8297 multiple-marker screening tests and database II contained the results of 1936 multiple-marker screening tests and fetal karyotypes. RESULTS: The overall screen-positive rate in database I was 7.1%; it was 7.5% in patients weighing <180 pounds and 5.1% in patients weighting ≥180 pounds (p = 0.001). Weight significantly affected the screen-positive rate only in women ≥30 years old (p = 0.003 for 30 to 34 years, p = 0.00004 for ≥35 years). A weight correction formula was derived; when applied to database II it eliminated individual weight-related differences but had no effect on the overall screen-positive rate or Down syndrome detection rate. CONCLUSIONS: Human chorionic gonadotropin concentration is affected by maternal weight. A weight correction formula eliminates individual weight-related differences in the screen-positive rate but has no discernible effect on the overall screen-positive or Down syndrome detection rates. © 1995.