The different effects of cytokines on cytosolic-free calcium concentration ([Ca2+]i) and intracellular stored calcium were investigated in platelets from 35 essential hypertensive patients (HT) and 45 age- and sex-matched normotensive control subjects (NT). Erythropoietin (EPO) and interleukin 2 significantly increased platelet [Ca2+]i, whereas platelet-derived growth factor, and fibroblast growth factor had no significant effect on [Ca2+]i. The EPO-induced rise of [Ca2+]i was significantly higher in HT compared to NT (15.2 +/- 4.3 nmol/L v 1.3 +/- 1.7 nmol/L, P < .01). Preincubation with EPO significantly increased calcium in intracellular stores in platelets from HT and NT. Inhibition of protein kinase C significantly enhanced EPO-induced rise of stored calcium. It is concluded that an increased response of HT to EPO may be associated with essential hypertension.