To investigate the relationship between sympathetic activity and blood flow in the kidney during propranolol treatment, 55 patients with uncomplicated essential hypertension were studied. Twenty-five of them had been treated with propranolol (average daily dose 240 mg) for about two weeks; the others served as untreated controls. In all patients renal arteriography was carried out, after which renal plasma flow (125I-hippuran clearance), cortical blood flow (xenon-washout), and renal release of norepinephrine and renin were measured. In the propranolol group, renal plasma flow had also been determined before treatment. Cardiac output (dye-dilution) and creatinine clearance were measured both before as well as during therapy. In untreated hypertensives renal cortical blood flow was reduced to about 80% of what was predicted for the age level. On the basis of their changes in blood pressure, patients who were treated with propranolol were divided into responders (n = 15) and nonresponders (n = 10). Despite a similar fall in cardiac output in both subgroups, renal blood flow remained unchanged in responders, while it fell in nonresponders. In addition, renal norepinephrine release was significantly higher in nonresponders than in responders, while renin release in nonresponders was markedly suppressed. It may be concluded that sympathetic activity is an important determinant of renal (cortical) blood flow in essential hypertension. The effect of propranolol on the renal circulation depends, to some extent, on its unmasking of prevailing alpha-adrenergic tone. However, when blood pressure falls, an additional mechanism may be operative to cause renal vasodilation.