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Early diagnosis and appropriate management of neonatal hyperbilirubinemia are very important in order to prevent bilirubin encephalopathy and kernicterus. Several diagnostic tests may be used for this purpose, including bilirubin level itself. The aim of the present study was to investigate whether serum alkaline phosphatase (ALP), which is an intracellular enzyme found abundantly in red blood cells, could be used for the early diagnosis and prediction of hyperbilirubinemia in newborns.A total of 100 babies were evaluated, starting from the sixth hour after birth, and serum ALP and bilirubin levels were analyzed.ALP levels were significantly higher in babies requiring therapy such as phototherapy or exchange transfusion (247.01 ± 67.44 IU/L vs 154.25 ± 56.07 IU/L). ALP levels rose significantly with rising total bilirubin level.ALP levels at the sixth hour of life may be a significant predictor of developing hemolysis and hyperbilirubinemia requiring treatment.