A chicken liver cDNA library was constructed in bacteriophage λgt10. A full-length transthyretin cDNA clone was identified by screening with rat transthyretin cDNA and was sequenced. A three-dimensional model of chicken transthyretin was obtained by computer-graphics-based prediction from the derived amino acid sequence for chicken transthyretin and from the structure of human transthyretin determined by X-ray diffraction analysis [Blake, C. C. F., Geisow, M. J., Oatley, S. J., Rérat, B. & Rérat, C. (1978) J. Mol. Biol. 121, 339–356]. The similarity of the amino acid sequences of chicken and human transthyretins was 75% overall and 100% for the central channel containing the thyroxine-binding site. Also, the organization of the transthyretin gene into exons and introns and the tissue specificity of expression of the transthyretin gene were similar in chicken and mammals, despite an evolutionary distance of about 3 × 108 years from their common ancestor, the Cotylosaurus. By far the highest levels of transthyretin mRNA were found in choroid plexus. The data suggest a fundamental role for the cerebral expression of transthyretin in all vertebrates. It has been proposed that this role is the transport of thyroxine from the bloodstream to the brain [Schreiber, G., Aldred, A. R., Jaworowski, A., Nilsson, C., Achen, M. G. & Segal, M. B. (1990) Am. J. Physiol. 258, R338–R345].