Paratuberculosis, which is also known as Johne's disease, is a chronic, progressive enteric disease of ruminants caused by infection with Mycobacterium paratuberculosis. Cattle become infected with M. paratuberculosis as calves but often do not develop clinical signs until 2 to 5 yr of age. The clinical disease is characterized by chronic or intermittent diarrhea, emaciation, and death. Although animals with clinical disease are often culled from the herd, animals with subclinical paratuberculosis may cause economic losses because of reduced milk production and poor reproductive performance. Although the economic impact of paratuberculosis on the national cattle industry has not been determined, it is estimated to exceed $1.5 billion/yr. The diagnosis of subclinical paratuberculosis is difficult. Bacteriologic culture is the most definitive method of diagnosis, but culture is time consuming and labor intensive. Serological assays are not very useful because animals do not develop an antibody response until the clinical stages of disease. Development of assays to measure cell-mediated immunity is critical to accurate detection of paratuberculosis in subclinically infected animals. Although not considered a zoonotic agent, M. paratuberculosis has been identified in intestinal biopsy tissue from patients with Crohn's disease, an inflammatory enteritis in humans. Currently, the potential human health risk is being addressed by research evaluating pasteurization of dairy products in the US.