Dystrophic cardiac calcification (DCC) is often found in DBA/2 mice, reportedly in association with low plasma magnesium levels in this mouse strain. It was hypothesized that high-phosphorus diets and low-magnesium diets that are known to lower plasma magnesium concentrations would promote the development of DCC. DBA/2 mice were fed diets with either low-magnesium (0.02%, w/w) or high-phosphorus (0.8%) concentrations or a combination of the two variables. NMRI mice were given either a low-(0.2%) or high-(0.6%) phosphorus diet. Female, but not male, NMRI mice accumulated calcium in the heart when fed the high-phosphorus diet; neither gender developed kidney calcification. DBA/2 mice with either a low-magnesium or a high-phosphorus intake developed marked cardiac calcifications. The combination of low-magnesium and high-phosphorus intake caused severe calcification of the heart, kidney and tongue'. Increasing the dietary magnesium content (0.08%) and reducing phosphorus (0.2%) did not fully prevent cardiac calcification, but reduced heart calcium concentrations in male DBA/2 mice. It is concluded that diets for DCC-susceptib1e mice should contain adequate amounts of magnesium and low, but sufficient amounts of phosphorus in order not to additionally stimulate cardiac calcification.