In mammals, islet amyloid polypeptide (IAPP) is a putative pancreatic peptide hormone that is coproduced and cosecreted with insulin in the beta-cells. However IAPP is also structurally and functionally similar to calcitonin gene-related peptide (CGRP), a 37-amino acid peptide that is expressed predominantly in neurones, and it has been suggested that these peptides arose from a common ancestral gene. In the present study we have characterized an avian IAPP cDNA and gene and have analyzed their expression in various tissues. The cloned chicken IAPP cDNA encodes a 135-amino acid (aa) precursor in which the mature 37-residue IAPP is 80% identical to human IAPP. However, the N-terminal propeptide of chicken proIAPP (55 aa) is considerably longer than that found in the mammalian proIAPPs (9-12 aa) and is comparable in length to that of chicken proCGRP (52 aa). Most of this additional peptide material was found to be encoded in an exon of the cloned chicken IAPP gene that is homologous to exon 3 in the CGRP gene. This exon is absent in the human IAPP gene and thus the exon-intron organization of the chicken IAPP gene more closely resembles that of mammalian CGRP genes. Northern blot analyses demonstrated that chicken IAPP mRNA is expressed predominantly in intestine and brain but at a much lower level in pancreas. The pancreas and intestine contained a single 0.7 kilobase (kb) IAPP transcript while two transcripts, 0.7 kb and 0.9 kb, were detected in brain. Densitometric analysis indicated that IAPP transcripts were 11 times more abundant in brain and intestine than pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)