Red blood (RBC) ionized magnesium (Mg2+) was determined by nuclear magnetic resonance (NMR) in order to assess the usefulness of this technique as an index of magnesium depletion. Twenty-four normal subjects underwent a 3-week low-Mg diet. The RBC Mg2+ fell from 209 +/- 9.8 microM before diet to 162 +/- 9.3 microM at the end of the 3 weeks (p < 0.001). In patient populations, 22 hypomagnesemic hospitalized patients had a significantly lower RBC Mg than normal (146 +/- 7.1 microM, p < 0.002), and 37 outpatients with diabetes mellitus had a mean RBC Mg2+ of 172 +/- 7.1 microM which was also significantly lower than normal (p < 0.001). These data suggest that determination of RBC Mg2+ may be used to reflect intracellular Mg status.