The renal catabolism of [125I]glucagon-like peptide 1 (GLP-1) and [125I]glucagon-like peptide 2 (GLP-2) has been studied both in vivo, by the disappearance of these peptides from the plasma of bilaterally nephrectomized (BNX), ureteral-ligated (BUL) or normal rats, and in vitro, analyzing their catabolism by the isolated, perfused rat kidney. Results from in vivo studies demonstrated that half-disappearance time for both peptides was lower in controls than in BUL rats, and this value in BUL rats was not significantly different from that in BNX rats. In addition, metabolic clearance rate of GLP-1 was higher in control rats than in the other two groups of animals. Urinary clearance rate of both peptides was negligible. In isolated kidney experiments, values for organ clearance of both [125I]GLP-1 and [125I]GLP-2 were similar to those of inulin clearance, which represents the glomerular filtration rate. Urinary clearance of trichloroacetic acid precipitable radioactivity represented less than 1% of total clearance. In conclusion, these results demonstrate a significant role for the kidney in the plasma removal of [125I]GLP-1 and [125I]GLP-2 by a mechanism that involves glomerular filtration and tubular catabolism.