Circulating substances that increase intracellular calcium, and other circulating substances that increase blood pressure, have been described in hypertensive animals and humans. In this study, we report the existence of a factor of the plasma of spontaneously hypertensive rats that does both. These effects were dose-dependent, and the time course for such effects was correlated with the time course for potentiation of pressor agents by the plasma. In addition, the plasma of spontaneously hypertensive rats was found to inhibit the depressor effects of parathyroid hormone. Our results confirm the presence of a circulating hypertensive factor in the plasma of spontaneously hypertensive rats, which may act by increasing calcium uptake in vascular smooth muscle. These findings may also help explain the secondary increase in parathyroid hormone noted in some forms of human and experimental hypertension.