BACKGROUND ABO incompatibility is now the most common cause of isoimmune hemolytic disease of the newborn here. Although hemolytic disease because of ABO incompatibility is clinically milder than that from Rh incompatibility, severe hemolysis occasionally occurs, and some cases require exchange transfusion. It is desirable to assess the accuracy of a group of tests to predict the development of neonatal hyperbilirubinemia in ABO incompatibility. Then, early treatment is available for minimizing the frequency of exchange transfusion. METHODS Eighty-eight healthy full-term newborn infants born to blood group 0 mothers were studied and divided into four groups. Each baby weighed 2.5 Kg or more, had no evidence of G-6-PD deficiency. Group 1 consisted of 29 blood group A or B infants with hyperbilirubinemia (serum bilirubin levels > or = 15 mg/dl) and/or icterus praecox. Group 2 consisted of 24 blood group A or B infants without hyperbilirubinemia (serum bilirubin levels < 15 mg/dl). Group 3 consisted of 7 blood group 0 neonates with hyperbilirubinemia. Group 4 consisted of 28 blood group 0 neonates without hyperbilirubinemia. Titers of maternal IgG anti-A and anti-B antibodies were measured. Cord blood was used to performed direct Coombs' test and for bilirubin level determinations. RESULTS A total of 18 (62.1%) mothers had IgG anti-A or anti-B titers > or = 512X in Group 1. The majority of mothers (91.5%) in Group 2, 3 and 4 had anti-A or anti-B titers < or = 128X. Thirteen (44.8%) neonates in Group 1 had positive direct Coombs' test of the cord blood. Only one neonate (4.2%) in Group 2 and one neonate (3.6%) in Group 4 had positive direct Coombs' test. A total of 12 neonates (41.4%) in Group 1 had cord bilirubin levels > or = 4 mg/dl, whereas none in the other groups had cord bilirubin levels > or = 4 mg/dl. CONCLUSIONS ABO incompatible newborn infants with maternal IgG anti-A or anti-B titers > or = 512X, cord bilirubin levels > or = 4 mg/dl or positive direct Coombs' test of the cord blood represent a "high risk" category, and should be placed in hospital where frequent re-evaluation and appropriate therapy are available.