The endangered Sonoran pronghorn (Antilocapra americana sonoriensis) consists of only 2 small populations, 1 in Arizona and 1 in Mexico. Mitochondrial DNA sequence data and 5 microsatellite loci were used to compare levels of genetic diversity and differentiation between the 2 Sonoran pronghorn populations and between this subspecies and other selected pronghorn populations, both proximate and distant to the Sonoran pronghorn's current range. The data support a history of recent isolation of Sonoran pronghorn populations from those in Arizona, New Mexico, and Texas. Loss of genetic diversity due to bottlenecks and drift has been severe in both populations of the Sonoran pronghorn, but is most pronounced in the Arizona population. These results are discussed in terms of conservation management strategies.