Amylin is a 37 amino acid hormone, co-secreted with insulin from the pancreatic β-cell in response to nutrient stimuli. Because the human amylin analog, pramlintide, is being tested in patients with diabetes mellitus, a known risk factor for nephropathy, we examined the role of the kidney on amylin and pramlintide metabolism and action in functionally nephrectomized rats. Nephrectomy markedly altered amylin metabolism: it increased incremental area under the plasma amylin concentration curve 3.6-fold (P < 0.001) and increased the elimination half-life from 17 ± 1 to 26 ± 2 minutes (P < 0.01) after subcutaneous injection of 100 µg amylin. Nephrectomy decreased plasma amylin clearance from 20.3 ± 1.1 to 7.9 ± 0.4 mL/min (P < 0.0001). Thus, at these doses in the rat, the kidney is important for metabolizing amylin and pramlintide.