In the winter of 2002, an outbreak of mycoplasma infection in Vaal rhebok (Pelea capreolus) originating from South Africa occurred 15 weeks after their arrival in San Diego, Calif. Three rhebok developed inappetence, weight loss, lethargy, signs related to pulmonary or arthral dysfunction, and sepsis. All three rhebok died or were euthanized. Primary postmortem findings were erosive tracheitis, pleuropneumonia, regional cellulitis, and necrotizing lymphadenitis. Mycoplasmas were detected in numerous tissues by electron microscopy, immunohistochemistry, and PCR. The three deceased rhebok were coinfected with ovine herpesvirus-2, and two animals additionally had a novel gammaherpesvirus. However, no lesions indicative of herpesvirus were seen microscopically in any animal. The rheboks' mycoplasmas were characterized at the level of the 16S rRNA gene, the 16S-23S intergenic spacer region, and the fructose biphosphate aldolase gene. Denaturing gradient gel electrophoresis was carried out to address the possibility of infection with multiple strains. Two of the deceased rhebok were infected with a single strain of Mycoplasma capricolum subsp. capricolum, and the third animal had a single, unique strain most closely related to Mycoplasma mycoides subsp. mycoides large-colony. A PCR survey of DNA samples from 46 other ruminant species demonstrated the presence of several species of mycoplasmas in the mycoides cluster, including a strain of M. capricolum subsp. capricolum identical to that found in two of the rhebok. These findings demonstrate the pervasiveness of mycoplasmas in the mycoides cluster in small ruminants and the potential for interspecies transmission and disease when different animal taxa come in contact.