We report the complete sequence of an extreme halophile,Halobacterium sp.NRC-1, harboring a dynamic 2,571,010-bp ge-nome containing 91 insertion sequences representing 12 familiesand organized into a large chromosome and 2 related minichro-mosomes. TheHalobacteriumNRC-1 genome codes for 2,630 pre-dicted proteins, 36% of which are unrelated to any previouslyreported. Analysis of the genome sequence shows the presence ofpathways for uptake and utilization of amino acids, active sodium-proton antiporter and potassium uptake systems, sophisticatedphotosensory and signal transduction pathways, and DNA repli-cation, transcription, and translation systems resembling morecomplex eukaryotic organisms. Whole proteome comparisonsshow the definite archaeal nature of this halophile with additionalsimilarities to the Gram-positiveBacillus subtilisand other bacteria.The ease of culturingHalobacteriumand the availability of meth-ods for its genetic manipulation in the laboratory, including con-struction of gene knockouts and replacements, indicate this halo-phile can serve as an excellent model system among the archaea.