Mitral valve prolapse syndrome (MVP) is a frequent disorder characterized by a number of complaints which lessen the quality of life. The pathogenesis of MVP symptoms has not been fully elucidated. Hyperadrenergic activity and magnesium deficiency have been suggested. This study was designed to verify the concept that heavily symptomatic MVP is accompanied by hypomagnesemia and to elucidate whether magnesium supplementation alleviates the symptoms and influences adrenergic activity. We assessed serum magnesium in 141 subjects with heavily symptomatic primary MVP and in 40 healthy controls. Decreased serum magnesium was found in 60% of patients and in 5% of controls (p <0.0001). Patients with low serum magnesium were subjected to magnesium or placebo supplementation in a double-blind, crossover fashion. Typical symptoms of MVP (n = 13), intensity of anxiety, and daily excretion of catecholamines were determined. After 5 weeks, the mean number of symptoms per patient decreased from 10.4 +/- 2.1 to 5.6 +/- 2.5 (p <0.0001), and a significant reduction in weakness, chest pain, dyspnea, palpitations, and anxiety was observed. Increased noradrenaline excretion before and after magnesium was seen in 63% and 17% of patients, respectively (p <0.01). Mean daily excretion of noradrenaline and adrenaline was significantly diminished after magnesium. It is concluded that many patients with heavily symptomatic MVP have low serum magnesium, and supplementation of this ion leads to improvement in most symptoms along with a decrease in catecholamine excretion.