The genomic sequence of the halophilic archaeon Halobacterium NRC-1 has been analyzed by the Z curve method. The Z curve is a three-dimensional curve that uniquely represents a given DNA sequence. Based on the known behaviors of the Z curves for the archaea whose replication origins have been identified, the analysis of the Z curve for the genome of Halobacterium NRC-1 strongly suggests that the large genome has two replication origins, oriC1 (921,863-922,014) and oriC2 (1,806,444-1,807,229), which are located at two sharp peaks of the Z curve. These two regions are next to the cdc6 genes and contain multiple copies of stretches of G and C, i.e., ggggtgggg and ccccacccc, which may also be regarded as direct and inverted repeats. Based on the above analysis, a model of replication of Halobacterium NRC-1 with two replication origins and two termini has been proposed. The experimental confirmation of this model would constitute the first example of multiple replication origins of archaea, which will finally provide much insight into the understanding of replication mechanisms of eukaryotic organisms, including human. In addition, the potential multiple replication origins of the archaeon Sulfolobus solfataricus are suggested by the analysis based on the Z curve method. (C) 2003 Elsevier Science (USA). All rights reserved.