Intracellular free (cytosolic) calcium has been reported to be increased in the platelets of patients with essential hypertension. We investigated the possibility that the high cytosolic calcium concentration may be caused by a circulating plasma factor, by incubating platelets from normotensive subjects with plasma ultrafiltrates from patients with essential hypertension. The cytosolic calcium concentration in normal platelets increased after incubation with plasma from patients with untreated hypertension (80 +/- 15 percent [+/- SEM]) or from patients in whom hypertension was well controlled by calcium-influx blockers (129 +/- 33 percent). In contrast, the cytosolic calcium concentration was unchanged after incubation with plasma from normotensive subjects. When platelets from the patients were incubated with plasma from the controls, cytosolic calcium in platelets decreased by more than 30 percent, into the normal range (P less than 0.01). These data demonstrate that plasma from patients with essential hypertension contains a substance that increases the cytosolic calcium concentration in platelets. Cytosolic calcium is a trigger for vascular smooth-muscle-cell contraction, and if the plasma factor acts on these cells as it acts on platelets, it may be responsible for the increased peripheral vascular resistance associated with hypertension.