To investigate the association of hypertension and insulin resistance, we utilized 31P-NMR spectroscopy to noninvasively assess intracellular free magnesium levels (Mgif) in erythrocytes of normotensive (n = 20) and essential hypertensive (n = 20) subjects given an oral 100 g glucose load. In hypertensive compared with normotensive subjects, fasting glucose and insulin levels were similar, but the integrated insulinemic responses to glucose were 45% greater (312 +/- 13.4 v 215 +/- 7.5 microU/mL, P less than .001). In hypertension, Mgif levels were significantly reduced (183 +/- 9 v 251 +/- 9 mumol/L, P less than .001), and for all subjects were closely and inversely related to systolic (r = -0.77, P less than .001) and diastolic (r = -0.81, P less than .001) blood pressures, and to the integrated insulin response (r = -0.72, P less than .001). Furthermore, while insulin responses were also related to the underlying systolic (r = 0.69, P less than .001) and diastolic (r = .73, P less than .001) pressures, these relations were no longer significant when adjusted for Mgif levels. We hypothesize that hypertension and peripheral insulin resistance may be different clinical expressions of a common abnormal intracellular ionic environment, characterized at least in part by suppressed levels of intracellular free magnesium.