Our aim was to assess the effectiveness of neonatal treatment of Rh hemolytic disease with high-dose intravenous immunoglobulin (HDIVIG), in reducing neonatal hemolysis. A total of 40 neonates born to isoimmunized Rh negative women were studied. The population was randomized into 2 groups: Group 1 received IVIG 800 mg/kg/day for 3 days, plus phototherapy; and Group 2 received only phototherapy. No significant difference was observed between the groups in the severity of either the antenatal and neonatal disease, mode of delivery, mean birthweight, gestational age at delivery, proportion of preterm deliveries, 1 minute Apgar Score, days of phototherapy, and presence of neonatal cholestasis. Group 1 babies showed a significantly decreased duration of hospitalization, less hemolysis, and a less marked increase in bilirubin levels on the first day of life than Group 2 newborns. Therefore, Group 1 neonates received less treatment with transfusions (exchange-transfusions and/or simple blood treatment with transfusions) than those in Group 2. Our data suggest that the frequency of transfusional therapy can be reduced by combining conventional phototherapy with HDIVIG. Further studies are needed to determine the optimum timing and dosages of neonatal HDIVIG treatment.