In considering the origin and evolution of proteins, the possibility that proteins evolved from exons coding for specific structure-function modules is attractive for its economy and simplicity but is not systematically supported by the available data. However, the number of correspondences between exons and units of protein structure-function that have so far been identified appears to be greater than expected by chance alone. The available data also show (i) that exons are fairly limited in size but are large enough to specify structure-function modules in proteins; (ii) that the position of introns for homologous domains in the same gene is reasonably stable, but there is also evidence for mechanisms that alter the position or existence of introns; and (iii) that it is possible that the observed relationship of exons to protein structure represents a degenerate state of an ancestral correspondence between exons and structure-function modules in proteins.