A first generation cosmid contig map of the Leishmania major Friedlin genome has been constructed, and genomic sequencing is well underway. Chromosome 1 (Chr1) and Chr3 have been completely sequenced, and Chr4 is virtually complete. Sequencing of several other chromosomes is in progress and the complete genome sequence may be available as soon as 2003. More than 600 completely sequenced new genes have been identified, representing approximately 8% of the total gene complement (approximately 8,600 genes) of Leishmania. Notably, a large proportion (approximately 69%) of the genes remain unclassified, with 40% of these being potentially Leishmania- (or kinetoplastid-) specific. Most interestingly, the genes are organized into large (>100-300 kb) polycistronic clusters of adjacent genes on the same DNA strand. Chr1 contains two such clusters organized in a 'divergent' manner, whereas Chr3 contains two 'convergent' clusters, with a single 'divergent' gene at one telomere, with the two large clusters separated by a tRNA gene. Statistical analyses of Chr1 show that the 'divergent junction' region between the two polycistronic gene clusters may be a candidate for an origin of DNA replication.