Pigs have been selected for high (H) or low (L) combined antibody and cell-mediated immune response to test the high immune response phenotype as a candidate for an indirect approach to improving health and productivity in livestock. Mycoplasma hyorhinis infection was induced in H and L pigs of the 4th generation of selection to test the hypothesis that immune response lines differ in response to infection. The major disease sign, arthritis, was more severe in the H pigs both clinically and at necropsy. M. hyorhinis was isolated at higher colony counts from synovial fluids of the H pigs. In contrast, pleuritis and peritonitis were less severe in pigs of the H than those of the L line. Pericarditis, although less in H than L pigs, did not differ significantly by line. Synovial fluid antibody to M. hyorhinis did not differ by line but H pigs produced serum antibody earlier and to a higher titre than did L pigs. Selection for H or L immune response therefore alters response to M. hyorhinis, however there is no indication of a consistent line-related health advantage.