The Francisella pathogenicity island (FPI) is a cluster of 16-19 genes, which is found duplicated in most of the Francisella genomes that have been sequenced. Although 16 FPI genes are highly conserved there are 2-3 putative genes that are absent or interrupted by stop codons in some strains. Francisella strains with experimentally induced mutations in FPI genes are highly attenuated in virulence and show defects in intramacrophage growth. There is experimental evidence indicating that the regulation of most FPI genes is affected by the presence of the virulence regulator MglA and by the concentration of iron in the growth medium. Although studies of mRNA expression show that essentially all FPI genes are transcribed, only a handful of FPI-encoded proteins have been detected by biochemical methods. The cumulative biochemical and genetic data to date have not yet been able to ascribe a biochemical function to any of the FPI-encoded proteins. However, bioinformatics analysis suggests that some of the FPI-encoded proteins are part of a type VI secretion system.