The Immunoglobulin IgG 1 and IgG 2 isotype immune responses of domestic ruminants and mice to Cowdria. ruminantium live infection or by immunization with inactivated organisms were determined by the enzyme linked immunosorbent assay and Western blotting. Immunization of goats with inactivated elementary bodies (IEBs) led to a predominant IgG 1 isotype response. This indicated that a Th2 response was induced. After challenge, the IgG isotype responses were mixed whereby both IgG 1 and IgG 2 antibodies were detected. Two goats that survived virulent challenge had a predominant IgG 2 isotype response. In cattle live infection by natural challenge or experiment led to a predominant IgG 1 isotype response. Immunization of cattle with IEBs however led to mixed IgG responses characterized by similar IgG 1 and IgG 2 ratios. In the mouse live infection led to a predominant IgG 2 isotype response. This indicated the mouse developed a true Th1 type cell mediated immune response when inoculated with live organisms. Immunization with inactivated organisms on the other hand led to a dominant IgG 1 response. It is evident from this work that the immune responses of ruminants and mice to C. ruminantium are different and that using mice as the experimental model for immune responses to Cowdria ruminantium. is not the appropriate.