T he bacterium Mycoplasma bovis is an economically important pathogen of cattle that contributes to the multifactorial bovine respiratory disease complex. In addition to causing respiratory disease, this bacterium can cause polyarthritis, mastitis, otitis media, and a chronic pneumonia-polyarthritis syndrome, impacting beef and dairy cattle worldwide (1). Despite increased recognition of its role in economic loss in the cattle industry, M. bovis remains a clinical challenge because of a common carrier state in clinically healthy animals, variable disease expression, intermittent shedding, and the lack of rapid accurate diagnostic assays (1,2). Clinical disease is not considered necessary to maintain M. bovis in populations, and M. bovis is commonly detected in asymptomatic adult feedlot cattle (2). Although the upper respiratory tract mucosa is a primary site for M. bovis colonization, presence of the bacterium in the lung is variable in occurrence and clinical manifestation. In 1 study, M. bovis was detected in 46% of cattle with normal lungs, 82% of cattle with acute fibrinous pneumonia, and 98% of cattle with chronic pneumonia (3). Manifestation of M. bovis-associated respiratory disease is particularly common in the wake of stress (e.g., from transportation, comingling, feedlot entry, and harsh temperatures or conditions). In the early 2000s, M. bovis caused several highmortality (case-fatality rate 45%) epizootics in bison (Bison bison) in North America (4). These events raised concern about emergent virulent strains, and research began to characterize isolates from different host species (5). An important difference between outbreaks of mycoplasmosis in bison and cattle is that, in the former, few or no co-infecting bacterial or viral pathogens are consistently detected (4,6-8). Although M. bovis virulence factors are poorly defined, evasion of immune response is implicated in maintaining chronic infection (9). One study found that that up to 79% of bison herds in western Canada have >1 M. bovis-seropositive animal and that 8 of 11 herds with no history of M. bovis disease had seropositive animals (10). These findings suggest that host response to M. bovis varies; some exposed bison become subclinical carriers and might also