To investigate whether serum in hypertensive Dahl salt-sensitive rats (S rats) contains a hypertensinogenic substance, we examined the effects of repeated injections of serum from such S rats on blood pressure (BP) and pressor responses. Serum was collected from either hypertensive or normotensive S rats (fed an 8% or 0.11% NaCl diet, respectively) and injected into uninephrectomized recipient S rats for 2 weeks (0.45 ml, twice a day, i.v.). Serum from hypertensive rats injected for 14 days significantly increased BP by 14 mm Hg (143 vs 129, p less than 0.05), pressor responses to angiotensin II (ANGII) by 45% (p less than 0.005), pressor responses to norepinephrine (NE) by 38% (p less than 0.025), and Na concentration in the aortic wall of recipient rats by 5.9% (p less than 0.05), compared to the effects of the injection of serum from normotensive S rats. These results imply that hypertensive S serum contains a hypertensinogenic substance and that this serum factor produces a mild hypertension in the recipient rats and also contributes importantly to the hypertension in donor S rats. Dahl salt-resistant rats (R rats) on either 8% or 0.11% NaCl had normal BP. Their sera produced no differences in BP or in pressor responses in recipient rats. Hence 8% NaCl, which produced no hypertension, also induced no hypertensinogenic serum factors in R rats. We sought to determine whether nephrectomy would alter these humoral factors. The BP averaged 139 mm Hg in rats receiving normotensive sham-nephrectomized S serum vs 154 in those receiving hypertensive sham-nephrectomized S serum, 15 mm Hg higher (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)