Technical Abstract: Johne's disease is a chronic, debilitating intestinal disorder in cattle characterized by diarrhea, reduced feed intake, weight loss and death. Cattle usually become infected as young calves by ingesting feces containing the causative bacteria. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced milk production by these animals, they also present a potential infective threat to the rest of the herd. Johne’s disease is difficult to diagnose and therefore to control. Development of accurate and sensitive diagnostic tests is dependent upon understanding the immune responses of the host animal during infection. This paper describes work that is currently being conducted on paratuberculosis by scientists within ARS. It is a multi-factorial approach to research with focus on understanding the immunology and pathogenesis of the disease in order to develop new tools for the detection of infection. It is also possible that this information will lead to new preventative and therapeutic regimes.