Abstract — — To investigate the role of intracellular potassium (K i )and other ions in hypertension and diabetes, we utilized 39 K-, 23 Na-, 31 P-, and 19 F-nuclear magnetic resonance (NMR) spectroscopy to measure K i , intracellular sodium (Na i ), intracellular free magnesium (Mg i ), and cytosolic free calcium (Ca i ), respectively, in red blood cells of fasting normotensive nondiabetic control subjects (n=10), untreated (n=13) and treated (n=14) essential hypertensive subjects, and diabetic subjects (n=5). In 12 subjects (6 hypertensive and 6 normotensive controls), ions were also measured before and after the acute infusion of 1 L of normal saline. Compared with those in controls (K i =148±2.0 mmol/L), K i levels were significantly lower in hypertensive (132.2±2.9 mmol/L, sig=0.05) and in type 2 diabetic subjects (121.2±6.8 mmol/L, sig=0.05). K i was higher in treated hypertensives than in untreated hypertensives (139±3.1 mmol/L, sig=0.05) but was still lower than in normals. Although no significant relation was observed between basal K i and Na i values, saline infusion elevated Na i ( P <0.01) and reciprocally suppressed K i levels (142±2.4 to 131±2.2 mmol/L, P <0.01). K i was strongly and inversely related to Ca i ( r =−0.846, P <0.001), and was directly related to Mg i ( r =0.664, P <0.001). We conclude that (1) K i depletion is a common feature of essential hypertension and type 2 diabetes, (2) treatment of hypertension at least partially restores K i levels toward normal, and (3) fasting steady-state K i levels are closely linked to Ca i and Mg i homeostasis. Altogether, these results emphasize the similar and coordinate nature of ionic defects in diabetes and hypertension and suggest that their interpretation requires an understanding of their interaction.