Genes that show complex tissue-specific and temporal control by regulatory elements located outside their promoters present a considerable challenge to identify the sequences involved. The rapid accumulation of genomic sequence information for a number of species has enabled a comparative phylogenetic approach to find important regulatory elements. For some genes, which show a similar pattern of expression in humans and rodents, genomic sequence information for these two species may be sufficient. Others, such as the cystic fibrosis transmembrane conductance regulator (CFTR) gene, show significant divergence in expression patterns between mouse and human, necessitating phylogenetic approaches involving additional species. The ovine CFTR gene has a temporal and spatial expression pattern that is very similar to that of human CFTR. Comparative genomic sequence analysis of ovine and human CFTR identified high levels of homology between the core elements in several potential regulatory elements defined as DNase I hypersensitive sites in human CFTR. These data provide a case for the power of an artiodactyl genome to contribute to the understanding of human genetic disease.