The gene coding for human prothrombin has been isolated from two human genomic DNA libraries using a human prothrombin cDNA. Present evidence indicates that the gene is approximately 24 kb in length with about 90% of the DNA representing intervening sequence. Thirteen intervening sequences were found to interrupt the region coding for the mRNA into 14 exons. These intervening sequences vary greatly in size and contain at least 11 copies of Alu repetitive DNA. The positions where several of the intervening sequences interrupt the coding region appear to separate functional and structural domains of the protein. A similar placement of intervening sequences in genes coding for proteins homologous to prothrombin has been observed and provides additional evidence that these proteins have evolved from a common ancestor.