We tested the hypothesis that overactivity of the renal and systemic renin-angiotensin system is important to the pathogenesis of hypertension in autosomal dominant polycystic kidney disease (ADPKD). Up to 21 normotensive subjects with ADPKD and creatinine clearance > 70 ml/min/1.73 m2 were compared to 12 unaffected controls from the same families. Blood pressure, serum chemistry, sodium excretion, plasma renin and serum aldosterone and atrial natriuretic peptide (ANP) levels were measured at baseline, after acute sodium depletion, and after chronic higher sodium intake with and without enalapril. Effective renal plasma flow was measured by paraaminohippurate clearance in the higher sodium state, before and during an intravenous infusion of angiotensin II at 3 ng/kg/min. This was to test whether, by analogy to non-modulating essential hypertension, renal blood flow would fall to a lesser extent in the ADPKD subjects. The groups were comparable at baseline apart from a higher supine mean arterial pressure in the ADPKD group (median 91 vs. 81 mm Hg, P = 0.002). There were no significant differences between ADPKD and control subjects in blood pressure or hormonal response to sodium depletion. During chronically higher sodium intake, serum ANP was significantly higher (median 130 vs. 81 ng/liter, P = 0.0006) and plasma renin tended to be higher (median 20.5 vs. 13.5, P = 0.08) in ADPKD than in control subjects. The ADPKD group had a higher renal vascular resistance (median 7420 vs. 5915 dyn.sec.cm-5, P = 0.009) before angiotensin, but tended to have a lower percentage rise in resistance during angiotensin (median 31.5 vs. 46, P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)