In preparation for gene manipulative experiments in mice we have isolated genomic clones covering the entire murine cathepsin K gene (Ctsk). Sequence analysis revealed that the gene spans 10.1 kb and contains eight exons and seven introns. The sizes of the coding exons 2–7 as well as the pattern of intron sizes are conserved between the human and mouse cathepsin K genes. Genomic organization of the mouse cathepsin K gene also closely resembles those of cathepsins S and L. More than 26% of the Ctsk sequence consists of different repetitive elements. Detailed sequence analysis of 1.7 kb of Ctsk promoter revealed several putative binding sites for transcription factors and two stretches of 280–320 bp which were >70% homologous with the human cathepsin K promoter. Analysis of genomic clones extending further upstream of the Ctsk gene identified the 3′ end of the gene coding for arylhydrocarbon-receptor nuclear translocator (Arnt). This places Ctsk approximately 4.5 kb downstream of Arnt on mouse chromosome 3 at locus 47.9.