Magnesium deficiency may play a role in the pathogenesis of atherosclerosis, cardiac arrhythmias, and coronary spasm. Because less than 1% of magnesium (Mg) is extracellular, the serum magnesium (sMg) does not always accurately reflect intracellular Mg stores. To determine the frequency of Mg deficiency in patients with cardiovascular disease, we measured blood mononuclear cell Mg content (mMg) and sMg concentrations in 104 unselected patients admitted to our intensive cardiac care unit (CCU). Twenty-seven normal healthy controls and 33 hypomagnesemic patients with chronic alcoholism and/or malabsorption syndrome served as reference groups. The sMg concentration in the CCU patients was 2.05 +/- 0.03 mg/dl (mean +/- SEM), and did not differ from normal controls (mean 2.01 +/- 0.03 mg/dl). Only 8 of 104 CCU patients were hypomagnesemic (7.7%). mMg in the CCU patients, however, was significantly lower than in the normal controls (1.15 +/- 0.02 micrograms/mg protein and 1.34 +/- 0.02 micrograms/mg protein respectively, p less than 0.001). Fifty-three percent (55 of 104) of CCU patients had mMg contents less than 1.119 micrograms/mg protein, i.e., below that of the lowest normal control. mMg was significantly lower in those patients with congestive heart failure (mMg = 1.08 +/- 0.03 micrograms/mg protein) when compared to those patients without congestive heart failure (1.23 +/- 0.02 micrograms/mg protein, p less than 0.001). We conclude that the incidence of intracellular Mg deficiency in patients with cardiovascular disease is much higher than the sMg would lead one to suspect, and may contribute to clinical cardiovascular morbidity.