The temporal changes in plasma leptin concentrations were studied in healthy adults who underwent unilateral nephrectomy. Another group who underwent abdominal surgery for repair of aneurysm or to relieve arterial stenosis, was also studied. Plasma leptin concentrations increased to 230% ± 74% of prenephrectomy levels at 8 to 16 hours after surgery and then generally declined. Subjects with prenephrectomy leptin concentrations above 14 μg/L maintained elevated postnephrectomy levels, whereas subjects with low prenephrectomy concentrations had final leptin levels below prenephrectomy concentrations. Abdominal surgery subjects did not manifest the increase after surgery, but generally had declining concentrations throughout the convalescent period. Free and bound fractions of plasma leptin and leptin binding capacity were measured in the prenephrectomy and peak specimens (8 to 16 hours postnephrectomy) by high-performance liquid chromatography (HPLC). The increase in total leptin postnephrectomy largely affected the free fraction of leptin, without significant increase in bound leptin or leptin binding capacity. We conclude that (1) plasma leptin concentrations increase acutely after nephrectomy, consistent with the role of the kidneys in eliminating circulating leptin; (2) plasma leptin concentrations decline thereafter, suggesting activation of compensatory elimination capacity; and (3) the postnephrectomy peak in total leptin increases primarily free leptin.