Experimental allergic orchitis (EAO) was induced in the rabbit by immunization with a partially purified testicular antigen (TCA) from rabbit or guinea pig (GP) in complete Freund's adjuvant. All rabbits immunized with rabbit TCA (RTCA) developed severe testicular disease early (day 10) whereas serum antibody to rabbit sperm was detected late (day 60). Immune complexes, with one exception, were not found in the testicular lesions. In contrast, rabbits immunized once with GPTCA developed high titers of serum antisperm antibody early (day 10) in association with focal and mild testicular lesions that were inconsistent. However, when rabbits were hyperimmunized with GPTCA (three injections), severe orchitis developed in association with peritubular immune complexes. The immune complexes, composed of sperm antigen, antisperm antibody of IgG and IgM classes and C3, were confined to the testis. Antibody from rabbits immunized with RTCA reacted with rabbitspecific sperm antigens, whereas antibody from GPTCA-immunized rabbit reacted in part with sperm antigens that were shared between rabbit and GP. The results indicate that 1) EAO can be readily induced in the rabbit, 2) rabbit EAO can be induced with testicular antigens of homologous or heterologous origin, 3) GP and rabbit antigens elicit antisperm antibody with different specificities, 4) the immunopathology of EAO induced by rabbit and GP antigens differs and suggests involvement of different pathogenetic mechanisms, and 5) in GP antigen-induced EAO, the findings are indistinguishable from those of postvasectomy orchitis in the rabbit.