Hypertension is common in patients with polycystic kidney disease (PKD). This study addresses the hypothesis that sympathetic activity is enhanced in hypertensive PKD patients, not only when renal function is impaired but also when renal function is still normal. Muscle sympathetic nerve activity (MSNA, peroneal nerve), plasma renin activity (PRA), heart rate, and BP were studied in PKD patients with normal and with impaired renal function and in matched controls. In hypertensive patients with normal renal function, MSNA and mean arterial pressure (MAP) were higher than in normotensive patients (23 +/- 5 versus 15 +/- 7 bursts/min; 110 +/- 10 versus 90 +/- 3 mmHg; P < 0.05), whereas PRA and heart rate did not differ. In PKD with chronic renal failure (CRF) (creatinine clearance rate, 39 +/- 19 ml/min), MAP, MSNA and PRA were higher than in controls (resp, 116 +/- 7 versus 89 +/- 9 mmHg; 34 +/- 14 versus 19 +/- 9 bursts/min; 405 [20 to 1640] versus 120 [40 to 730] fmol/L per sec; all P < 0.05). Heart rate in PKD CRF did not differ from controls. MSNA correlated with MAP (r = 0.42; P = 0.01) and age with MSNA (r = 0.45; P < 0.01). Regression line of age and MSNA in patients was steeper than that in controls. This study indicates that MSNA is increased in hypertensive PKD patients regardless of renal function. The data support the idea that sympathetic hyperactivity contributes to the pathogenesis of hypertension in PKD.