A high calcium intake has been shown to attenuate the degree of hypertension in spontaneously hypertensive rats (SHR) and some human hypertensives. Conversely, a low calcium intake has been associated with an increase in blood pressure in both groups. In the present study, the effects of a high (2%), medium (0.6%) and low (0.02%) calcium diet on mean arterial pressure (MAP) and on the expression of a novel circulating hypertensive factor--parathyroid hypertensive factor (PHF)--were examined in SHR. In rats on the low calcium diet, MAP and PHF activity were significantly higher at 8 weeks than in the other two groups. In the high calcium group, MAP was significantly lower than in the other two groups, although it was elevated compared to week 0 values. PHF activity was not detected in the plasma of this high calcium group. Overall, MAP was highly correlated with PHF activity (r = 0.78, P = .0001). These results suggest that the effects of dietary calcium on blood pressure in SHR may be mediated by a novel circulating hypertensive factor, PHF, such that a high calcium diet inhibits, and a low calcium diet stimulates, the expression of this factor.