Swine mycobacteriosis (tuberculosis) is a common cause of carcass condemnation in major swine production areas. Once the infection is established in a swine herd it is difficult to effectively prevent or eliminate the disease. Evaluation of in situ mRNA cytokine profiles of lymphoid tissue in swine mycobacteriosis has not previously been performed. The inflammatory cytokine mRNA expression of inflammatory cytokines (TNF, IL-1, IL-6 and IL-8) in lymphoid tissues of swine experimentally infected with M. avium serovar 2 was compared to non-infected swine lymphoid tissue and evaluated by morphological localization of cytokine mRNA using in situ hybridization at 160 days post-infection A marked increase in TNF mRNA expression, mild increase in IL-8 mRNA expression and mild increase in IL-1 mRNA expression was detected in mandibular lymph nodes from infected swine compared to non- infected swine. A mild increase in IL-6 mRNA expression was also observed in tonsils from infected swine. Cytokine mRNA was detected in macrophages and lymphocytes primarily within cortical follicles and adjacent mantle zones. The inflammatory cytokine mRNA expression profile appears altered in infected swine lymphoid tissue possibly by local factors present on, or secreted by, M. avium. Altered cytokine expression could delay or prevent an appropriate immune response capable of effective clearance and prevention of disease. These results suggest that alterations in cytokine mRNA expression are important in the pathogenesis and clinical course of swine mycobacteriosis. (Am J Vet Res 2000; 61:1487-1491)