Initial exposure of the mother to the Rh antigen occurs most often during parturition, miscarriage, abortion, and ectopic pregnancy. Invasive investigative procedures such as amniocentesis, chorionic villus sampling, and fetal blood sampling also increase the risk of fetal transplacental hemorrhage and alloimmunization. Recognition of the antigen by the immune system ensues after initial exposure, and reexposure to the Rh antigen induces a maternal anamnestic response and elevation of specific IgG-Rh antibody. Active placental transport of this antibody and immune attachment to the Rh-antigenic sites on the fetal erythrocyte are followed by extravascular hemolysis of erythrocytes within the fetal liver and spleen. The rate of the hemolytic process is proportionate in part to the levels of the maternal antibody titer but is more accurately reflected in the antepartum period by elevation of the amniotic fluid bilirubin concentration and in the postpartum period by the rate of rise of unconjugated bilirubin. In contrast to ABO incompatibility, the greater antigenicity and density of the Rh-antigen loci on the fetal erythrocyte facilitates progressive, rapid clearance of fetal erythrocytes from the circulation. A demonstrable phase of spherocytosis will be absent. Compensatory reticulocytosis and shortening of the erythrocyte generation time, if unable to match the often high rate of hemolysis in utero, results in anemia in the newborn infant and a risk of multiple systemic complications.