Skeletal muscle biopsy and autopsy samples of 132 SLE patients were studied by immunofluorescence and light microscopic techniques. Immune deposits were compared to histologic abnormalities and clinical and serologic findings. Immune deposits with a mainly granular pattern were observed at different locations in 49 patients (37%). They correlated significantly (p<0.001) with inflammatory myopathy, demonstrated in 33(25%), with noninflammatory myopathy which occurred in 38 (29%) vasculitis, observed in 13(10%), and with noninflammatory vasculopathy which was noted in 10 patients (8%). The correlation of muscle immune deposits with anti-DNA antibodies was significant at p= 0.016. Anti-Sm and anti-U1 RNP antibodies were associated significantly with the intensity of immune deposits. Furthermore, a correlation of immune deposits with increased creatine phosphokinase and myopathic electromyogram, but not with evidence of clinical involvement, was shown. A key pathogenetic role of immune deposits in the development of skeletal muscle histologic abnormalities in SLE was demonstrated.