The osteocalcin (OC) gene was initially described as a single copy gene encoding the bone specific vitamin K dependent and vitamin D regulated protein. We report here the presence of multiple copies of the gene in mouse and rat. Southern blot analysis and restriction mapping of genomic DNA from several strains of mice indicated the presence of at least three copies of the OC coding sequence within a 19 kb fragment. Two closely linked OC genes contain the proximal promoter region with intact coding sequences. The third potential OC gene includes a 3.5 kb insert between an OC promoter-like region and a coding region that has several amino acid substitutions distributed among functional domains when compared with the normal gene. The 940 nucleotides upstream of the modified coding region lack the well defined 5' regulatory elements that support basal and hormone-responsive transcriptional control. In rats either one or more OC genes were observed in different strains or in Sprague Dawley rats obtained from different suppliers.