Inoculation with hemagglutination-positive (HA+) cultures of Mycoplasma synoviae AAY-4 induced acute synovitis significantly more frequently (P = 0.001) in chicken tibiotarsal-tarsometatarsal joints than did inoculation with HA-negative (HA-) cultures derived from the same clone of AAY-4. Immunoblotting analyses showed that HA+ cultures abundantly expressed two phase-variable hemadherence-associated surface membrane proteins of 53 kDa and 48 to 50 kDa defined by monoclonal antibodies. HA- cultures lacked the 53-kDa proteins and synthesized truncated 27- to 30-kDa forms of the 48- to 50-kDa proteins. Inoculation of cyclosporin A (CsA) into infected joints significantly decreased the frequency of acute synovitis (P = 0.001). Moreover, repeated intra-articular inoculation of CsA (three doses of 1 mg at 2-day intervals) significantly reduced the local antibody response to M. synoviae in the joints treated with CsA.