The effects of magnesium supplementation were tested in 20 patients with essential hypertension receiving long-term thiazide diuretic treatment (Th group) and 21 age-matched untreated patients (EHT group). Intra-erythrocyte cations, water content and the ouabain-sensitive sodium efflux rate constant were measured. The Th group received magnesium supplementations as MgO (600 mg Mg/day) for 4 weeks. In the Th group intra-erythrocyte magnesium and the sodium efflux rate constant were lower and red cell sodium was higher than in the EHT group. During magnesium supplementation, there were significant decreases (p less than 0.01) in intra-erythrocyte sodium content and mean blood pressure, and increases (p less than 0.005) in red cell magnesium content and the sodium efflux rate constant. These effects of magnesium were more evident in 9 patients who were unresponsive to diuretic therapy, a definite reduction in mean blood pressure, from 104.8 +/- 2.7 mmHg to 94.4 +/- 2.2 mmHg (p less than 0.001), being observed. In the remaining 11 patients, however, blood pressure remained unchanged. The sodium efflux rate constant was positively correlated with red cell magnesium content and negatively correlated with sodium content (r = 0.61, p less than 0.005 and r = -0.57, p less than 0.01, respectively). These results indicate that long-term diuretic treatment may give rise to intracellular magnesium deficiency and a suppression of cell membrane active sodium transport. The results also suggest that oral magnesium may decrease intracellular sodium, possibly through the activation of Na-K-ATPase, which in turn may contribute to the reduction in blood pressure. Therefore, magnesium supplementation may be a worthwhile additional therapy for diuretics.