Mycoplasma arthritidis was demonstrated to incite experimental conjunctivitis and uveitis in Swiss Webster mice which have a known susceptibility to the arthritis customarily associated with infection by this mycoplasma. The initial symptom of ocular involvement was conjunctivitis, which appeared as early as 1 day after intravenous injection with viable culture concentrates of M. arthritidis. By day 2, histological analysis showed intraocular localized inflammatory reactions that were confined primarily to the anterior portion of the uvea and produced results which were compatible with those seen in iridocyclitis. Serological assays of the titer and the class of antibodies involved in the early humoral immune response to infection confirmed the predominance of immunoglobulin G (IgG) concentrations over IgM concentrations that was described by others (Cole et al., Infect. Immun. 4:431-440, 1971) and revealed significant titers of the IgG2a and IgG2b subclasses of complement-fixing antibodies. The rapid onset of acute conjunctivitis, together with the early appearance of immunoglobulins of the IgG class, suggests that the M. arthritidis-infected Swiss Webster mice may have experienced an anamnestic response to the mycoplasma antigens. These observations introduce a new animal model for the study of mycoplasma-induced experimental uveitis and conjunctivitis, which are demonstrated here to accompany a disseminated systemic disease process.