Recent prospective study of intravenous magnesium sulphate administration into patients with acute myocardial infarction revealed the improvement of survival rate of these patients. This study was designed to determine the effect of intravenous administration of magnesium on the renin-angiotensin-aldosterone (RAA) system. MgSO4 (0.72% in 3.24% glucose solution) at 5 mEq/hr was infused intravenously into six healthy normotensive men for six hours. MgSO4 infusion increased plasma renin activity (PRA) at 60 minutes (4.1 +/- 1.4 ng/ml/hr vs 2.7 +/- 0.8 ng/ml/hr, p < 0.05) and decreased plasma aldosterone concentration (PAC) at 180 minutes (40 +/- 8 pg/ml vs 60 +/- 12 pg/ml, p < 0.05). The maximum level of serum magnesium reached 2.32 +/- 0.09 mEq/L, from the control value of 1.58 +/- 0.07 mEq/L, at -3 hours. Analysis of both serum levels and urinary excretion of electrolytes revealed significant increases in urinary excretion of calcium and magnesium, whereas no significant changes in other electrolytes in serum or urinary excretion were found. To clarify the mechanism by which magnesium increased PRA and suppressed PAC, either prostaglandin synthesis inhibitor, indomethacin (75 mg/day), or a calcium channel blocker, diltiazem (90 mg/day), was administered. Indomethacin completely blocked the increase in PRA but did not induce any changes in PAC. Diltiazem inhibited the decrease in PAC but did not induce any changes in PRA. These data indicate that magnesium stimulates renin release through the elevation of prostaglandins and suppresses aldosterone production through the intracellular calcium mobilization. From these results it is suggested that a favorable effect of magnesium administration to patients with myocardial infarction relates to the alterations of the RAA system.