As far as we know, humans are the only known natural hosts for M. pneumoniae disease. Whereas volunteer studies have provided useful data on the pathogenesis of disease and efficacy of vaccines, experimentally inducing disease in humans raises serious ethical questions and has become increasingly difficult to defend. Thus, there is a genuine need for a satisfactory animal model to study M. pneumoniae disease. Using the cotton rat and developing chick embryo models, Eaton and co-workers (9-13) have clearly shown that the infectious "Eaton agent" was the cause of primary atypical pneumonia. After the causative agent was identified as M. pneumoniae (14), more definite and quantitative studies were possible. The hamster animal model has provided most of our information on the pathogenicity of strains, the pathogenesis of disease and the potency of inactivated vaccines. However, protective data obtained in hamsters immunized with the TS mutant vaccines did not correlate with data obtained in humans, raising concern regarding the use of the hamster animal model to evaluate the potency of live TS vaccines. The chimpanzee animal model has a number of advantages. Chimpanzees become clinically ill, show positive X-ray findings, and develop cold agglutinin titers. In fact, the experimentally induced disease in chimpanzees is remarkably similar to naturally occurring primary atypical pneumonia in patients. Because of the close genomic relationship, immunologic reagents prepared and used for human studies can also be used successfully in chimpanzee studies. The chimpanzee model also has some serious disadvantages. They are expensive to house and maintain and are generally not available to the scientific community. Nonetheless, chimpanzees are probably the best, most meaningful animal models established thus far to examine the infectious process, the immune response and the pathogenesis of this disease and to determine approaches to effective therapy and immunization of diseases produced by known pathogens, like M. pneumoniae, as well as reputed mycoplasma pathogens, such as M. genitalium and M. hominis.