To elucidate the antihypertensive mechanism of oral calcium supplementation in salt-dependent hypertension, we investigated the hypertensive activity of plasma from DOCA-salt hypertensive rats fed with (DS-Ca) or without (DS) a high calcium diet. Four weeks of calcium supplementation (4% CaCl2) attenuated the blood pressure increase in DS rats. Intravenous bolus injection of dialyzed plasma (1.0-kDa cutoff) from DS rats to normotensive rats resulted in a sustained elevation in blood pressure, whereas that from DS-Ca rats did not. As the endothelin concentration was not different between the two groups, the circulating hypertensive substance in DS rats may be identical to parathyroid hypertensive factor (PHF) and the inhibition of its expression by calcium may be involved in the hypotensive mechanism of high calcium diets in salt-dependent hypertension.