Objective:To determine the clinical relevance of the newly described circulating pressor factor with parathyroid hypertensive factor (PHF)-like activity.Design:Plasma samples were collected from 94 normotensive and 93 essential hypertensive subjects, the latter either previously defined by dietary salt sensitivity (n = 43), or prospectively studied on both low- (<50 mmol/day) and high-salt (>200 mmol/day) diets (n = 16).Methods:Blood pressure, demographic factors, plasma renin activity (PRA), urinary electrolyte excretion and bioassayable PHF-like activity were determined in the fasted state on basal and altered dietary salt intakes.Results:Among the normotensive subjects significantly higher PHF-like activity and reciprocally lower PRA values were observed in Black versus Caucasian subjects, particularly among females. In the hypertensive subjects PHF-like activity levels were significantly elevated in the low- (17.1 ± 1.5 mmHg, n = 34) and normal- (6.7 ± 1.8 mmHg, n = 36) but not in the high-renin subgroups compared with values in the normotensive subjects (1.6 ± 1.1 mmHg). Similarly, PHF-like activity values were significantly higher in salt-sensitive than in salt-insensitive hypertensives. Prospectively, PHF-like activity rose significantly with salt loading (4.9±1.2 to 20.4±6.2mmHg) and was positively related (r = 0.648,P< 0.001) to the pressor response to salt.Conclusions:Elevated levels of PHF-like activity are characteristic of the low-renin or salt-sensitive state, or both, and may contribute to the hypertensive process. Elevated PHF-like activity levels found in normotensive subjects may presage the development of low-renin, salt-sensitive hypertension.