The initial injection of guinea pigs with homologous retina led to uveitis of maximal severity within 3–4 weeks which slowly diminished in intensity with time, but was still present at 20 weeks. Complement-fixing (CF) antibodies were detected in the large majority of animals with uveitis, and declined in parallel with the subsiding course of the disease. Reimmunization during the phase of antibody decline resulted in acute relapse of uveitis in approximately half of the animals, even though clinical evidence of persisting chronic ocular inflammation was present. Relapse was limited to those with little or no circulating CF antibody remaining at the time of reinjection, and occurred in a large majority of such animals. Those with CF antibody titers greater than 1/10 failed to relapse, although the anamnestic responses indicated stimulation of the immune mechanism. Results indicate that CF antibodies prevented reinduction of the disease and represent a potentially protective response.