Hyperglycosylated hCG (H-hCG) is a minor variant of hCG with abnormal oligosaccharide side chains. It is the principal gonadotropin detected in the serum and urine of patients with gestational choriocarcinoma. A monoclonal antibody was produced against this antigen and an immunoassay developed. Levels of hCG and H-hCG were determined in 142 urine samples from normal pregnancies from 10 to 21 weeks of gestation. Levels were normalized to urine creatinine concentration, and were each plotted against gestational age. Bi-weekly median values were calculated, the best-fitting regression lines were determined, and multiples of the normal median (MoM) were computed. 10 Down syndrome pregnancy samples were tested from 11 to 21 weeks of gestation. The median hCG and H-hCG levels in the Down syndrome cases were 1.9 MoM and 5.7 MoM of unaffected cases, respectively. Four of 10 hCG measurements and 9 of 10 H-hCG determinations exceeded the 95th centile of unaffected cases. H-hCG identified 90 per cent of Down syndrome cases with a 5 per cent false-positive rate. This is more than twice the number of cases detected by an hCG assay. H-hCG may be an effective replacement for hCG in antenatal Down syndrome screening. This is a preliminary report consisting of only 152 samples. Further studies are needed now to verify the Down syndrome screening utility of this potentially valuable new marker.