A common feature of mycobacteria is they induce a wide spectrum of immunological responses in infected animals. We have therefore examined both the antibody response by ELISA and the T cell response using a gamma interferon assay in cattle infected with M. bovis or M. paratuberculosis. The predominant immune response in cattle is a cellular response and the interferon assay had a sensitivity of 93% for bovine tuberculosis and 73% for Johne's disease. In contrast, less than 50% of TB infected cattle had a detectable antibody response to an M. bovis culture filtrate antigen preparation. With Johne's disease infected cattle the level of humoral response as detected by the absorbed ELISA increased as the disease progressed. In subclinical animals not shedding bacteria in their feces, 16% were antibody positive, compared to 40% of subclinical fecal shedders, and 77% of animals with clinical disease. Because of this broad spectrum of immune responses, particularly with Johne's disease, we recommend that assays for both antibody and T cell reactivity be used in the control of Johne's disease in infected cattle herd.