This chapter focuses on red cell alloimmunization that is the immune-mediated destruction of erythrocytes initiated by maternal red cell antibodies which reach the fetal circulation by transportation across the placenta, onwards from approximately 12 weeks' gestation. Hemolytic disease of the newborn (HDN) describes the consequences of the antenatal pathogenic process which continues on into the newborn period. Prevention of Rhesus D (RhD) isoimmunization, and improvements in the ante-natal and neonatal care of isoimmunized women and their babies, has all but eradicated serious morbidity and mortality associated with this condition. Exogenous anti-D is produced by exposing RhD negative volunteers to the RhD antigen. The use of intravenous immunoglobulin is well established now in the treatment of neonatal alloimmune thrombocytopenia and HDN. Phenotypic tests of RhD status examine how blood from an individual behaves when it is added to serum containing anti-D antibodies.