Mycoplasma hyopneumoniae (M. hyo), the cause of enzootic pneumonia in swine, is a worldwide problem. Despite the developmental vaccines that have been commercially available for several years, M. hyo-induced pneumonia is still a major concern to swine producers. The pathologic lesions observed with enzootic pneumonia consist primarily of a lymphoid cell infiltration of the lungs. Four groups of pigs consisting of challenge control, vaccinated and challenged, vaccinated only, and nonvaccinated and non-challenged were used in this study. Lymphocytes from the peripheral blood, lung, and bronchial lymph nodes were analyzed by flow cytometry (FACs) to determine the populations of cells activated by M. hyo. No significant difference in percentages of B or T lymphocytes was found between the vaccinated and nonvaccinated groups. An ELISPOT assay was used to evaluate the isotype of antibodies secreted by B lymphocytes from the same tissues. Total secreted immunoglobulin and mycoplasmal membrane specific immunoglobulin secretion were measured. A significant increase in secretion of total IgG by lymphocytes in the lungs of pigs only challenged with M. hyo, and vaccinated/challenged was observed. No mycoplasma-specific stimulation was observed. The mycoplasmal membrane preparation induced a non-specific stimulation by IgM secreting cells in all groups. Again, no mycoplasma-specific response was observed. These results suggest that although IgGsecreting lymphocytes are stimulated to secrete antibodies in infected pigs, the lymphocyte response observed in enzootic pneumonia may not be to the M. hyo membrane antigen. At this time, it is unknown whether the immune response to M. hyo is predominately an antibody- or cellmediated immune response, and how these immune responses contribute to protection from enzootic pneumonia.