We investigated whether Doppler measurement of the fetal middle cerebral artery peak systolic velocity can be used to detect fetal anemia in pregnancies complicated by maternal blood group immunization. We first studied normal values for the middle cerebral artery peak systolic velocity in 135 fetuses (Group A), and also in 23 fetuses at risk for anemia who underwent 56 cordocenteses to assess the fetal hematocrit (Group B). A test to detect fetal anemia, based on the middle cerebral artery peak systolic velocity, was developed by using the data of the fetuses of Group A and Group B. Successively, the middle cerebral artery peak systolic velocity was prospectively determined in 16 fetuses at risk for anemia who underwent 42 cordocenteses (Group C) to assess the test developed, in a multicenter prospective fashion, by using the data of Group A and Group B. In the normal fetuses an exponential model expressed the increase of the middle cerebral artery peak systolic velocity values with advancing gestation. By using the data of the fetuses of Group A and Group B, four zones of anemia risk were identified. In Group C, none of the anemic fetuses had the middle cerebral artery peak velocity below the normal mean value, whereas all of the anemic fetuses had the peak velocity above the normal mean. The middle cerebral artery blood velocity increases with advancing gestation and is a non-invasive method of detecting anemia in pregnancies complicated by maternal blood group immunization.