Skeletal muscle from (New Zealand black x New Zealand white)F1 and MRL-lpr/lpr mice was examined for histopathologic abnormalities. Although young animals had no muscle abnormalities, older mice in both strains had the following histopathologic abnormalities: perimysial/endomysial inflammation, acute simple denervation, muscle degeneration/necrosis, and an increase in internal nuclei. MRL-lpr/lpr mice had the following additional histopathologic abnormalities: inflammatory vascular disease (vasculitis), central myofibrillar loss, fascial inflammation, and tubular aggregates. These abnormalities are comparable with those seen in human connective tissue diseases, particularly the association with inflammation. These mouse strains provide good animal models for the study of immunopathologic processes of skeletal muscle associated with connective tissue disease.