In vivo microscopic observations were made on arterioles and venules (10-20 microns i.d.) of the rat cremaster muscle circulation, using an image-splitting eyepiece and high-resolution TV image-intensification, in order to determine the microvascular effects of inorganic and organic magnesium (Mg) salts. MgSO4, MgCl2, Mg aspartate HCl, and Mg acetate were administered perivascularly and intravenously. Topical application (10(-2) to 10(1) mumol) and intravenous (i.v.) administration (5-400 mumol/kg/min) of all Mg salts, [which resulted in elevated plasma Mg levels (1.1-4.7 mg/dl over controls)], brought about rapid, almost instantaneous vasodilation of both arterioles and venules in low doses. Intravenous administration of Mg salts resulted in elevation of plasma calcium (0.5-1.5 mg/dl over controls) and decreases in plasma phosphate (0.5-1.2 mg/dl below controls); plasma Na and K were not affected. High doses (i.e. 400 mumol/kg/min) of some Mg salts, administered i.v., tended to constrict these microvessels. Diastolic and systolic arterial blood pressure as well as heart rate decreased in a dose-dependent manner upon systemic administration of all 4 Mg salts. Intravenous administration of high doses of the Mg salts (i.e., greater than 200 mumol/kg/min) often resulted in marked falls in mean arterial blood pressure (e.g. 110 to 40 mmHg) and heart rate (e.g. 460 to 130 bpm), followed by death. Administration of a variety of pharmacological antagonists and a cyclo-oxygenase inhibitor did not interfere with vasodilatation of arterioles or venules induced by Mg salts. Use of hyperosmolar sucrose partially mimicked some of the vasodilator, but not the cardiac or blood pressure lowering actions of Mg salts. These data indicate that magnesium ions: 1) bring about vasodilatation without releasing adrenergic amines, histamine, serotonin, acetylcholine, prostaglandins, or endogenous opioids; 2) are direct, potent vasodilators of intact rat cremaster muscle microvessels; 3) may have a depressive action on heart; 4) exert these microvascular and cardiac actions in low doses and 5) can produce severe hypotension and bradycardia only after i.v. administration of high doses. In addition, acute administration of various Mg salts can rapidly alter certain plasma electrolytes (e.g., Ca, PO4), at least in rats, which may be related to the microvascular actions of Mg2+.