Yorkshire pigs were bred selectively for high and low immune responses (H and L pigs, respectively) based on multiple antibody (Ab) and cell-mediated immune response traits. In a previous experiment, generation 4 (G4) pigs of each line were infected with Mycoplasma hyorhinis. High responders had a more rapid and higher Ab response and less polyserositis, but arthritis was more severe in H pigs than in L pigs. To test the hypothesis that line differences were attributable to differential expression of cytokines, M. hyorhinis infection was induced in pigs of G8. Arthritis was more severe clinically (P, 0.05) and postmortem (P, 0.001) when M. hyorhinis CFU were more numerous in synovial fluid (SF) of H pigs than of L pigs (P, 0.03). In H pigs but not L pigs, CFU and lesion scores were correlated positively. In H pigs, infection increased the frequency of expression of mRNAs for interleukin-8 (IL-8), IL-10, and tumor necrosis factor alpha (TNF-) in mononuclear cells from synovial membranes (SM). In L pigs, IL-1, IL-6, IL-10, and TNF- mRNAs were increased in frequency of expression. The quantity of the cytokine message for IL-6 was increased in infected H pigs. For L pigs, infection increased the cytokine message for IL-1, IL-6, IL-10, and TNF-. IL-6 in SM and gamma interferon (IFN-) in SF were produced at a higher copy number in H pigs than in L pigs after infection. For H pigs, there were no positive rank correlations between lesion or CFU scores and cytokines. For L pigs, IL-1, IL-8, IL-10, and TNF- in SM correlated with CFU, while IL-6, TNF-, and IFN- in SF correlated with CFU. Lesion score in L pigs correlated with IL-1 in SF. While these results indicate that H and L pigs differ in the cytokine response to M. hyorhinis infection, they do not confirm a characteristic cytokine response in association with the relative susceptibility to infection and arthritis observed in H pigs.