The study comprised 2,361 with two consecutive normal uncomplicated pregnancies screened at 15-20 weeks gestation for maternal serum alpha-fetoprotein levels (AFP). In 1,816 of these women, maternal serum human chorionic gonadotropin (hCG) levels were tested as well. The proportion of women who had a second high AFP level (greater than or equal to 2.0 MOM) in their subsequent pregnancy was 6.5-fold higher as compared with the proportion of women who had normal levels of AFP in their first tested pregnancy, The relative chance of having a second positive result of a low level of AFP (AFP less than or equal to 0.5 MOM) in subsequent pregnancies was 3.8-fold higher The relative chances of having a second positive result of high or low levels of hCG were 3.9- and 2.2-fold higher, respectively. It is concluded that there is a predisposition for abnormal levels of serum markers that is influenced by genetic and/or environmental factors, Therefore it is suggested that the individual's risk of having a Down syndrome baby, or other adverse pregnancy outcome that is derived from the serum markers' levels, should be adjusted taking into account unexplained high or low levels in previous pregnancies, A screening policy is suggested which is designed to yield a lower false-positive rate without affecting the detection rate of abnormal pregnancies. More data are needed before an accurate adjustment based on previous results can be made. (C) 1996 Wiley-Liss, Inc.