The influence of long-term alterations in dietary magnesium intake on blood pressure and on the antihypertensive effect of the calcium antagonist nifedipine was investigated in normotensive Wistar-Kyoto (WKY) and in spontaneously hypertensive rats (SHR). The rats were fed a diet either high (1%), normal (0.1%), or low (0.01%) in magnesium for 12 weeks (WKY) and 20 weeks (SHR), respectively. Nifedipine was added to the diet for 4 weeks in concentrations of 300 and 1000 ppm. Each dose was given for 2 weeks. Plasma and intraerythrocytic concentrations of sodium, potassium, and magnesium were measured before and at the end of nifedipine treatment. Blood was obtained by cardiac puncture. In the WKY and SHR, blood pressure was not influenced by magnesium intake. The blood pressure-lowering effect of nifedipine was most pronounced on normal dietary magnesium and was significantly suppressed in the magnesium-deficient rats. Plasma and intracellular total magnesium concentrations were consistently increased during high and reduced during low dietary intake of the ion. Intracellular sodium concentration increased during magnesium deficiency and was normalized by nifedipine. The marked and long-term alterations in plasma and intracellular concentrations of magnesium did not influence arterial blood pressure levels in either the normotensive WKY or the SHR. Therefore, dietary magnesium intake does not appear to play an important role in long-term regulation of blood pressure in rats. However, magnesium depletion attenuates the blood pressure-lowering effect of nifedipine.