Two of three groups of Patagonian cavies (Dolichotis patagonum) contracted Otodectes cynotis infestations after exposure to mite-infested feral cats. Otodectes cynotis infestations were initially identified in 9 of 10 cavies in group 1. Multiple feral cats with O. cynotis infestations were observed in the vicinity of the Patagonian cavies and were subsequently removed. The Patagonian cavies were initially treated with ivermectin (0.4 mg/kg s.q.) every 2 wk, but ivermectin was discontinued after the third treatment due to injury to one of the Patagonian cavies during capture. Sixteen months after initial treatment, clinical signs of scratching the pinnae, hemorrhagic lesions on the ear margins, head shaking, and O. cynotis mites in the auricular canal were again noted in all Patagonian cavies in group 1. Repeated administration of ivermectin (0.4 mg/kg s.q. every 2 wk for three treatments) failed to eliminate the mites in two of the Patagonian cavies. Selamectin administered (20 mg/kg, topically between the shoulder blades) to all Patagonian cavies eliminated the mite infestation after a single application. The Patagonian cavies remained O. cynotis mite free for 2 yr, until males (group 2) and females (group 3) were separated for population control. Three months after separation, 8 of the 12 females in group 3 again were infestated with O. cynotis mites. Feral cats with O. cynotis infestations were again noted in the vicinity of group 3. A single dose of selamectin applied topically eliminated all mites in all treated Patagonian cavies. Group 2 was not exposed to feral cats and remained mite free.