Amyloid deposition is a very typical alteration in the islets of Langerhans in human Type 2 (non-insulin-dependent) diabetes mellitus and in feline diabetes mellitus. Amyloid infiltration is also commonly found in insulin-producing pancreatic tumors. It was shown recently that amyloid purified from an insulinoma was composed mainly of a novel polypeptide (insulinoma amyloid polypeptide, IAPP), which had partial identity with the neuropeptide calcitonin gene-related peptide (CGRP). Cat islet amyloid contained a similar polypeptide. This finding is verified in the present study, and it is shown that the cat IAPP differs from the human peptide only in two of the 16 elucidated amino acid residues. The authors now also show by N-terminal amino acid sequence analysis that human islet amyloid is of IAPP origin. Although the significance of IAPP is unknown, its occurrence in pancreatic endocrine tissue and partial identity with a known neuropeptide suggests an endocrine regulatory function.