Dilated cardiomyopathy is one of the leading abnormalities in Emery-Dreifuss Muscular Dystrophy (EDMD). The pathogenesis of heart involvement in EDMD is, however, unknown. Autoimmune mechanisms have also to be taken into account. The aim of this study was to search for the presence of anti-heart antibodies in EDMD patients. The anti-heart auto-antibodies were detected in serum of 14 EDMD patients (the X-linked and the AD-Autosomal Dominant form). The control groups comprised 10 patients with Dilated Cardiomyopathy (DCM) and 10 healthy subjects. To screen serum for anti-heart antibodies against ventricular muscle proteins, they were separated by polyacrylamide gel electrophoresis, followed by Western blotting. In EDMD and DCM, IgG anti-heart antibodies against heart ventricular proteins were detected. In both diseases, 85 kD protein appeared to be the most immunogenic. Anti-troponin I (24 kD), anti-tropomyosin (35 kD) and anti-actin (43 kD) reactivity was less intense. There were significant differences in the reactivity of auto-antibodies between both EDMD forms, and also between EDMD and the DCM patients. No clear-cut correlation between the reactivity and frequency of the antibodies and clinical parameters of the EDMD patients was detected. The anti-heart proteins are reliable markers of immune involvement in dilated cardiomyopathy in the course of EDMD. Short- and long-term follow-up may define the role of anti-heart antibodies in predicting the susceptibility at risk of dilated cardiomyopathy in EDMD patients.