The intravenous and oral pharmacokinetics and the hepatic extraction ratio of pindolol were determined in 24 hypertensive patients with normal or impaired renal function. In patients with normal renal function, the total clearance was the sum of equal parts of the renal and nonrenal clearances. The nonrenal clearance was found to be equal to the hepatic clearance directly measured from the hepatic extraction ratio. Compared to patients with normal renal function, patients with chronic renal failure exhibited (i) unchanged K12 and K21 and nonrenal clearances, and (ii) significantly decreased values in half-life of the beta phase, Kel, and total renal clearance. The renal clearance was positively correlated (P less than 0.01) to the creatinine clearance. Bioavailability was significantly reduced (P less than 0.01) in the patients with renal failure. Assuming that the nonrenal clearance was equal to the hepatic clearance, the study provides evidence that, in patients with renal insufficiency, (i) no increased metabolism accompanies the decrease in renal function, and (ii) decreased availability is due to reduced absorption.