Maternal serum alpha-fetoprotein (MSAFP) concentration values were measured in relation to maternal age and fetal sex in the 16th to 20th gestational weeks in samples taken from 9,556 pregnancies with the outcome of live, mature and healthy infants. Our results show positive significance between MSAFP concentration and maternal age (p < 0.001); we also found significantly higher AFP values in male fetuses than in female fetuses (p < 0.001). This specificity is by all probability due to the change in the physiologic AFP concentration of the pregnant woman. Considering maternal age and the new percentile AFP values, cut-off concentration values can be corrected, thus the quality of routine AFP screening can be improved. At the same time, with the application of the above parameters, a more effective selection of pregnancies at high risk for Down syndrome can be achieved.