To examine further the potential role of intracellular cations in hypertension a nested case-control study was carried out in conjunction with a population-based survey. Based on a house-to-house sampling scheme, 43 hypertensive and 56 normotensive black residents of Maywood, IL, were recruited. Free cytosolic calcium (Cai) and intracellular stores of calcium after stimulation with ionomycin were determined in platelets with the fluoroprobe Indo-I; intracellular sodium (Nai) measured at rest and after incubation with ouabain was estimated with SBFI. Cell sodium content was also assayed in erythrocytes. Resting Cai and Nai were not different in hypertensives compared with normotensives, although ionomycin-stimulated levels of Cai were correlated with systolic blood pressure (r = 0.3; P = 0.04). A consistent set of inter-relations among the various cation parameters was observed, lending support to the hypothesis that the cellular metabolism of sodium and calcium may be linked in the pathophysiological pathway to hypertension.