Glutamate plays a critical role in the hypoxic ischaemic neuronal death. Two mechanisms of glutamate- induced neuronal death have been identified. One is rapid cell death that occurs in minutes and the second is delayed cell death that occurs over hours and is initiated principally by the activation of the N-methyl D-Aspactate (NMDA) receptor. Magnesium (Mg) is an NMDA receptor blocker. Systemic administration of Mg after a simulated hypoxic ischaemic insult has been shown to limit neuronal injury in several animal models. However, before embarking on to the use of Mg for neuronal protection in the human neonate it is important to study the safety and side effects of Mg administration.Forty terms, appropriate for gestational age babies with severe birth asphyxia (1 min Apgar score < 3 and 5 min Apgar score < 6), were randomly assigned to either the study group or the control group. Infants in both groups were treated as per unit protocol except that babies in the study group received intravenous injection of magnesium sulphate 250 mg/kg within half an hour of birth and subsequently 125 mg/kg at 24 and 48 hours of life.The mean cord blood serum Mg levels were 0.78 (+/- 0.047) mmol/L in the control group and 0.779(+/-0.045) mmol/L in the study group. The serum Mg levels at 3, 6, 12, 24, 48 and 72 hours of life were 1.87(+/-0.6), 1.65(+/-0.059), 1.468 (+/-0.91), 1.881 (+/- 0.053), 1.916 (+/- 0.053) and 1.493 (+/- 0.084) mmol/L respectively in the study group. All these values were significantly higher than those obtained in the control group (p< 0.001). No significant alterations in heart rate, respiratory rate, oxygen saturation and mean arterial pressure were seen, following magnesium infusion with either 250 mg/kg or 125 mg/kg dose. The serum Mg levels in the study group ranged between 1.493 (+/- 0.084) and 1.916(+/-0.053) mmol/L, which are considered to be in the neuroprotective range.Injection MgSO4 administered in a dose of 250 mg/kg and 125 mg/kg as an intravenous infusion is safe and the Mg levels obtained are in the range considered to be neuroprotective.