Superoxide dismutase (SOD: EC1.15.1.1) has been shown to increase in Down syndrome (DS) subjects and in amniotic fluid from DS affected pregnancies. In order to verify a possible increase of maternal serum SOD in DS affected pregnancies and its possible contribution in prenatal screening, the serum enzyme activity was retrospectively measured in samples from normal and DS affected pregnancies. Alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated oestriol (uE3) and serum SOD were measured in serum samples collected from 80 normal and 9 DS affected second-trimester pregnancies. The maternal serum SOD activity in the DS group (3. 12+/-0.73 U/ml) was significantly higher (p<0.001) than in the control one (2.20+/-0.7 U/ml). The addition of SOD appeared to be capable of improving the sensitivity of the conventional multi-parametric test (AFP, uE3 and hCG) even if the small number of subjects did not allow the achievement of statistical significance.