Carrion's disease is caused by infection with the ␣-proteobacterium Bartonella bacilliformis. Distribution of the disease is considered coincident with the distribution of its known vector, the sand fly Lutzomyia verrucarum. Recent epidemics of B. bacilliformis infections associated with atypical symptomatology in nonendemic regions have raised questions regarding the historic and present distribution of this bacterium and the scope of disease that infection causes. Phylogenetic relationships and genomic diversity of 18 B. bacilliformis isolates (10 isolates from a region where Carrion's disease is epidemic, Cuzco, Peru, and 8 isolates from a region where Carrion's disease is endemic, Caraz, Peru) were assessed using genomic data generated by infrequent restriction site PCR and gene sequence analysis of the flagellin gltA and ialB genes. A population genetic analysis of the genomic diversity suggests that what was once considered an epidemic region of Peru did not result from the recent introduction of B. bacilliformis.Bartonella bacilliformis, the causative agent of Carrion's disease (also referred to as bartonellosis, Oroya fever, and verruga peruana), has one of the highest reported human casefatality rates among bacterial diseases (e.g., 40 to 88% [12,24]). The classic disease is considered biphasic: the first phase involves a hemolytic anemia and fever, which occurs soon after infection, and this is followed by a cutaneous or verruga phase, which involves skin eruptions and can occur months after infection. Another distinctive feature of Carrion's disease is that the distribution of reported human disease has historically been considered to be restricted to a relatively well-defined altitudinal zone (600 to 3,200 m) of the Andean mountain valleys of South America (3, 17). It has been widely presumed that the limited geographic distribution was a function of the limited range of the sand fly vector, Lutzomyia verrucarum (3, 18). However, recent reports have documented human B. bacilliformis infections over a much larger area than previously reported, including the Andean highlands and the Amazona region east of the Andes mountains, as well as in historically recognized areas where B. bacilliformis is endemic (1, 9, 16, 17). These studies have indicated that in addition to B. bacilliformis occurring over a broader geographical range than previously recognized, the spectrum of symptoms associated with B. bacilliformis infection is highly variable.This extended range for human B. bacilliformis-associated disease suggests one or more possible scenarios of significant public health importance, including the following: (i) B. bacilliformis-associated disease has existed for many years over a much wider range than previously recognized; (ii) in addition to its endemic distribution, B. bacilliformis has a large but less stable distribution that results from multiple, overlapping introductions of the bacterium via frequent migration between endemic regions and regions that are only marginally capable of maintaining t...