Plasma levels of ionized magnesium (IMg) measured by ion-selective electrode were investigated in neonatal hyperbilirubinemia by comparing the newborns with ( greater than or equal to205 muM) and without (<205 muM) significant hyperbilirubinemia (groups of severe and moderate hyperbilirubinemia, respectively). Serum bilirubin, plasma IMg, and ionized calcium (ICa) levels were determined in 165 healthy term newborns with nonhemolytic indirect hyperbilirubinemia during the first 10 d of life. Mean serum bilirubin, plasma IMg, and ICa levels were 200.1 +/- 126.5 muM, 0.54 +/- 0.12 mM, and 1. 15 +/-.12 mM, respectively, in 165 newborns whose mean postnatal age was 156.1 +/- 46.5 h, and there was a significant positive correlation between the mean serum bilirubin and plasma IMg levels (r = 0.535, p < 0.001). Serum bilirubin levels (304.4 +/- 83.8 muM versus 94.1 +/- 54.7 muM) and plasma IMg levels (0.6 +/- 0.12 mM versus 0.49 +/- 0.1 mM) were significantly higher and plasma lCa levels (1.13 +/- 0. 2 mM versus 1.18 +/- 0.12 mM) were significantly lower in the group of severe hyperbilirubinemia (n = 83) when compared with the group with moderate hyperbilirubinemia (n = 82). Seventeen of the 83 cases of severe hyperbilirubinemia had IMg levels above the normal range ( greater than or equal to0.69 mM), whereas none of the 82 cases of moderate hyperbilirubinemia had elevated lMg levels. Fifteen of the 17 with high IMg levels had bilirubin levels >290 muM. Results of the present study suggest that increase in plasma lMg may be due to extracellular movement of Mg, a principally intracellular ion, resulting from generalized cellular injury including neurons and erythrocytes. Considering neuroprotective functions and beneficial effects of Mg ion in improving neurologic outcome, we also may speculate the possibility of a neuroprotective role or a compensatory mechanism in lMg increase against emerging toxicity risk of increasing serum bilirubin levels.