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The distribution and degradation of corticotrophin-(1–24)-tetracosapeptide specifically labelled with tritium at Tyr², Phe⁷ or Tyr²³ and [D-Ser¹, Lys¹⁷, Lys¹⁸]-corticotrophin-(1–18)-octadecapeptide amide labelled at Tyr² were studied at various times after intravenous injection into rats. By characterizing the radioactivity in plasma and various tissues, an overall picture of the metabolic handling of the two peptides emerged. The peptides left the circulation rapidly, entering mainly muscle and skin where they were extensively degraded. The D-Ser¹-containing analogue was less rapidly degraded and intact peptide persisted in muscle and skin for up to 1 h. This peptide probably returned to the circulation giving rise to the sustained plasma levels observed after injection of the D-Ser¹-substituted octadecapeptide but not after injection of the tetracosapeptide. Although initially the kidneys did not clear such large amounts of peptide as did muscle and skin they played an important role by continuously and, on the basis of existing evidence, irreversibly clearing the peptides and peptide fragments from the circulation and degrading them.