An 18 month old intact miniature jack, and a 2 year old Poitou jenny were donated to the Cornell University Large Animal Hospital in August 2011 to conduct a clinical trial of Ponazuril for the treatment of besnoitiosis. Besnoitia, an apicomplexan protozoan, was diagnosed via muscle biopsies in both donkeys prior to presentation. The donkeys originated from two separate farms in Pennsylvania, approximately 30 miles apart. Physical examination findings revealed generalized white miliary papules of the skin, mucosa, and conjunctiva of both donkeys. The jenny was also cachexic and weak. Fecal floatation revealed strongyles in the jenny. Skin biopsies prior to treatment confirmed Besnoitia species. Immunological testing, complete blood count, and chemistry panels were unremarkable. Ponazuril, an equine antiprotozoal drug, was instituted for 28 days without resolution or improvement of clinical signs. There is currently no effective treatment or cure for benoitiosis in donkeys.