OBJECTIVE: Our purpose was to determine whether parenteral magnesium sulfate crosses the rat placenta and enters the fetal brain. STUDY DESIGN: Twenty-eight pregnant female Long-Evans rats were divided into four groups, seven animals in each group. These groups included the following: single saline solution injection group evaluated after 20 minutes (control), single magnesium sulfate injection (270 mg/kg) evaluated after 20 minutes, and prolonged (2 and 4 hours) serum magnesium elevation (270 mg/kg loading and then 27 mg/kg every 20 minutes for maintenance). Each animal was killed, and maternal and fetal sera, amniotic fluid, and specific brain areas were analyzed for levels of magnesium. Statistical analysis included analysis of variance, multiple comparison procedure, and linear regression analysis. RESULTS: All three regimens of maternal subcutaneous magnesium sulfate resulted in significantly elevated maternal serum magnesium concentrations (p < 0.01). Fetal blood magnesium concentration rose from 3.9 +/- 0.3 to 4.9 +/- 0.1 mg/dl after 2 hours of continuous injections (p < 0.05), and to 5.3 +/- 0.0 mg/dl after 4 hours (p < 0.01). Amniotic fluid magnesium concentrations rose from 4.2 +/- 0.2 to 5.1 +/- 0.1 mg/dl after 4 hours (p < 0.05). Maternal blood magnesium concentrations were. significantly correlated with amniotic fluid concentrations (r = 0.59, p < 0.01). Four hours of maternal magnesium sulfate treatment resulted in a 25% increase in magnesium concentrations in the fetal forebrain (38.3 +/- 2.3 to 47.9 +/- 3.5 mg/dl/gm, p < 0.05). No significant changes in magnesium concentrations were detected in hindbrain. CONCLUSION: Magnesium sulfate injected subcutaneously into rats crosses the placenta within 2 hours of sustained magnesium levels, enter the fetal blood-brain barrier, and concentrates in the forebrain.