The rheumatic disease autoantigen, Ro/SSA, was immunogenic to a rabbit host. The heteroimmune rabbit serum bound the Ro/SSA particle in immunoblots and in an ELISA. Both the rabbit anti-Ro/SSA and a human prototype anti-Ro/SSA serum also bound IgG; and moreover, IgG inhibited both rabbit and human anti-Ro/SSA activity. Anti-IgG activity of the rabbit and human anti-Ro/SSA sera bound Ro/SSA by Western blot and solid-phase assays. In addition, purified Ro/SSA inhibited the anti-IgG activity of the anti-Ro/SSA sera from rabbit and man. Affinity purification of the IgG- and Ro/SSA-binding fractions of the rabbit anti-Ro/SSA demonstrated that both the anti-Ro/SSA and anti-IgG activities were concentrated in these fractions. These data show that Ro/SSA and IgG share epitopes that are bound by anti-Ro/SSA antibody. Inhibition experiments suggest that this antibody is found in most human anti-Ro/SSA autoimmune sera and that the epitope(s) are found in the F(ab')2 fragment of IgG.