Data from clinical cases, abattoir and serologic surveys have documented a substantial prevalence of paratuberculosis in Louisiana. Studies of cattle with chronic ruminant paratuberculosis have utilized histologic techniques to support in vivo and in vitro assays of immunological function. Dermal hypersensitivity, lymphocyte blastogenesis, Interleukin-1 and IL-2 assays have indicated the presence of various immunological perturbations during the chronic disease. Peripheral blood macrophages spontaneously release Interleukin-1 and this offers a possible explanation for the absence of concurrent or secondary disease. Studies of M. paratuberculosis strain 18, yielded the isolation of 2 or 3 different components which inhibited killing of Candida albicans by LPS-PMA activated adherent peripheral blood macrophages. The in vivo activity of these factors has been supported by growth of viable bacilli in activated bovine macrophage cultures. Murine infections at 8 weeks yielded viable organisms with evidence of ineffective lymphoid stimulation. These results suggest a mechanisms for the occurrence of regional granulomatous disease without systemic immunosuppression and for the ability of infected cattle to resist secondary diseases.