Naturally occurring mycoplasmal arthritis in various animals species and the ability to induce mycoplasmal arthritis experimentally have been the main reasons for searching for evidence of mycoplasmal infection in the joints of patients with rheumatoid arthritis. However, reliable reports of the isolation of mycoplasmas from synovial fluids and tissue of such patients do not exist, and measurements of specific antibodies have not proved rewarding. There is some evidence that infection by Mycoplasma pneumoniae occasionally has an arthritic sequela, although the microorganism has not been isolated from the joints of immunocompetent patients. In contrast, this and other mycoplasmas, including ureaplasmas, have been isolated from the arthritic joints of several hypogammaglobulinemic patients, and there is some evidence to indicate that the organisms are responsible for the disease. A relationship between mycoplasmas and sexually acquired Reiter's disease is unproven, but deserves thorough investigation in view of the link between ureaplasmas and nongonococcal urethritis. Furthermore, as new media and techniques become available, the possibility the mycoplasmas may have some role in rheumatoid arthritis should be reappraised.