Experimental autoimmune myositis (EAM), was produced in SJL/J mice by injection of an emulsion of crude syngeneic muscle homogenate and complete Freund's adjuvant (CFA). Nearly all injected SJL/J mice showed necrotic muscle fibres associated with infiltrating mononuclear cells, both within the necrotic fibres and in surrounding endomysial connective tissue. The disease in SJL/J mice was confined to skeletal muscle. Eight other mouse strains of different major histocompatibility types, similarly injected, failed to develop EAM. Direct immunofluorescence staining revealed prominent IgG deposition at the muscle cell membrane and in perimysial and endomysial connective tissue. This staining was present in both involved muscle of immunized SJL/J mice as well as in undamaged muscle from other immunized strains. Circulating anti-muscle antibodies as detected by indirect immunofluorescence staining of normal muscle were also present in both SJL/J mice and non-susceptible strains. An enzyme-linked immunosorbent assay (ELISA) was also developed for detection of serum anti-muscle antibody activity. Three strains of mice, including SJL/J, failed to develop significantly elevated anti-muscle antibody activity after injection of muscle and CFA, whereas six other strains that did not demonstrate histological myositis developed a 10-to 20-fold elevation of anti-muscle antibody activity. These results suggest that the ability to produce anti-muscle antibodies after immunization does not determine susceptibility to histological disease. Although EAM has been previously induced in other species, there have not been previous descriptions of this experimental disease in mice. This murine model may provide new insight into the immunopathogenesis of human inflammatory myopathies.