Experimental autoimmune orchitis (EAO) was induced in SMA mice (H-2nondefined) by repeated injection at intervals of 30 days of syngeneic testis homogenate (TH) together with Klebsiella O3 lipopolysaccharide (KO3 LPS) as a potent adjuvant. EAO was not induced by repeated injection of TH alone or KO3 LPS alone. At 10 days after the secondary injection of TH + KO3 LPS, there was marked infiltration with neutrophils in the seminiferous tubules and in the interstitium of the testis accompanied by destruction of the architecture of the seminiferous tubules and hypospermatogenesis. At 20 days after the secondary injection, infiltration with neutrophils in these areas had been replaced mostly by mononuclear cells (lymphocytes, plasma cells, and macrophages). Histopathological changes of the testes became severer by further injections until the 10th injection. The EAO lesions in the terminal stage were characterized by complete destruction of the tubular architecture of the testis, fibrosis, and aspermatogenesis. Lesions in the terminal stage were not restored at all. Spermagglutinating antibody titers in the serum increased and delayed-type hypersensitivity against TH estimated by footpad swelling developed in mice injected repeatedly with TH + KO3 LPS. Using immunofluorescence, antibodies against acrosomal components and tail components of the spermatozoa were detected in serum of these mice.