Magnesium is a potential neuroprotective agent in the treatment of head injury and ischemia whose efficacy is likely determined by increases in brain extracellular fluid (ECF) magnesium, which in turn depends on its concentration in plasma. The objectives of this study were to:1) examine the effects of increasing plasma magnesium concentration ([Mg]plasma) to 4-6 mM on brain ECF magnesium concentration ([Mg]ECF) and2) determine whether maturational changes occur in the transfer of magnesium into brain ECF for newborn and more mature (approximately 1 month old) miniswine. Increases in [Mg]plasmaby systemic administration of MgSO4resulted in similar maximal elevations in brain [Mg]ECFfor both age groups (193 ± 76%versus253 ± 106% of control for newborn and 1-month-old miniswine, respectively). Calculations of half-lives (t1/2) for the increase and decrease in magnesium concentration (t1/2uptake and t1/2clearance) were used to characterize magnesium kinetics in plasma and brain ECF. Plasma magnesium uptake was shorter in 1-month-old (t1/2= 11.1 ± 0.9 min) compared with newborns (12.9 ± 1.7 min,p< 0.05). The faster increase in [Mg]plasmaprobably contributed to a faster uptake of brain [Mg]ECFin 1-month-old compared with newborn swine (t1/2uptake = 27.9 ± 12.8versus46.0 ± 20.9 min, respectively,p< 0.05). Although plasma magnesium clearance was shorter in 1-month-old swine compared with newborn (t1/2= 34.3 ± 7.0versus74.7 ± 33.7 min, respectively,p< 0.05), the clearance of magnesium from the brain ECF was similar for each age group. Reductions in blood pressure and heart rate occurred during hypermagnesemia and were similar in each age group. This study shows that acute elevations in [Mg]plasmato 4-6 mM result in similar relative increases in brain [Mg]ECFfor both newborn and 1-month-old miniswine. However, there are maturational differences, as demonstrated by the faster rate of magnesium uptake into the ECF observed in the older miniswine.