Universal administration of an ion exchange column prepared Rh immune globulin (RhIG-IV) antepartum at 28 weeks' gestation and postpartum to 9,295 Rh negative women delivering Rh positive babies has reduced the prevalence of Rh immunization from the expected 601 to 25 (a protection rate of 95.9%). Rh immunization, despite universal Rh prophylaxis, developed in 25 women; eight before antenatal prophylaxis was administered, 17 after antenatal prophylaxis was administered. Residual Rh immunization is caused by small fetal transplacental hemorrhages (TPH) (greater than or equal to 0.01 mL of fetal blood) before antenatal prophylaxis (15%) and by significant fetal TPH (greater than or equal to 0.05 mL of fetal blood) between 30 and 38 weeks' gestation (18%); TPH was too great, in some instances, for residual passive Rh antibody to give protection. Although a reduction of 62% (five of eight) of early Rh immunization and 82% (14 of 17) of later Rh immunization might be achieved by addition of 16 weeks' to 20 weeks' gestation and 34 weeks' gestation Rh prophylaxis; and a reduction of 84% overall (21 of 25) might be achieved by universal fetal TPH screening every 2 weeks from 10 weeks' gestation until delivery, with administration of RhIG when a small early fetal TPH or a significant later fetal TPH is detected, all of these programs are costly in terms of prevention of perinatal mortality and in terms of cost per quality adjusted life year gained. We believe that the costs outweigh the benefit that would be achieved. Therefore, a residual Rh immunization prevalence of 0.24% to 0.31% during or after each Rh positive pregnancy in patients at risk is to be expected despite universal 28 weeks' gestation antenatal and postnatal Rh prophylaxis.