In humans, the kidney is involved in leptin clearance from the body. The present study was performed to assess the renal extraction of leptin in hypertensive patients with or without renal artery stenosis. Sixty-five hypertensive subjects (39 males and 26 females) underwent catheterization of the renal artery and both renal veins with blood sampling for measuring leptin levels. Blood flow to both kidneys was measured by the xenon washout technique. From these data, renal leptin uptake and renal fractional extraction of leptin were calculated. Endogenous creatinine clearance ranged from 24 to 191 ml/min in the males and from 20 to 149 ml/min in the females. In 25 patients, radiological signs of renal artery stenosis were present. Total renal leptin uptake by both kidneys averaged 141 ± 47 ng · min¹ · 100 g¹. No differences in leptin uptake were found between males and females or between patients with or without renal artery stenosis. The average renal extraction fraction of leptin was 6 ± 2%. Renal leptin uptake and renal extraction fraction of leptin did not correlate with arterial leptin concentrations or with blood pressure, endogenous creatinine clearance, or the presence or absence of renal artery stenosis. In hypertensive patients with or without renal artery stenosis, the kidney removes only a small fraction of circulating leptin from the body within one passage. This fraction remains relatively constant despite wide variations in renal function or circulating leptin.