We investigated the affect of cordocentesis (n = 36) and intravascular transfusion (n = 14) performed with a fixed needle guide on maternal serum alpha-fetoprotein levels. In 50% of the procedures, the placenta was anterior and punctured. For all patients, maternal serum alpha-fetoprotein levels rose 70.8% +/- 28%. The magnitude of the rise was unrelated to the number of attempts necessary, gestational age, or the initial maternal serum alpha-fetoprotein levels concentration. The location of the placenta was the sole identified variable related to the rise. A total of 44% of the patients had a significant increase in maternal serum alpha-fetoprotein level when the placenta was anterior. In contrast, only 4% of the patients had a significant rise in maternal serum alpha-fetoprotein level when the placenta was other than anterior. There was no difference in the frequency of a significant rise in maternal serum alpha-fetoprotein level concentration between the patients who underwent cordocentesis and those who underwent intravascular transfusion. On the basis of these findings, we recommend that when maternal isoimmunization is a potential concern and the placenta is anterior, the umbilical cord should be approached either through a window or laterally from the placenta.