Burkholderia pseudomallei is the etiologic agent of the tropical disease melioidosis and is considered to be a potential biological weapon. Two B. pseudomallei-like species, Burkholderia oklahomensis and Burkholderia thailandensis, have been described in the literature. Infections with both of these microorganisms have occurred in the United States, but little is known about the relative virulence of these isolates in animal models of infection. In this study, B. oklahomensis and B. thailandensis CDC2721121 were determined to be avirulent in hamsters and mice at all challenge doses examined. The virulence of B. thailandensis CDC3015869, on the other hand, was more similar to the virulence of isolates of B. thailandensis from Southeast Asia.