Chronic myocarditis predisposes to the occurrence of spontaneous ventricular arrhythmias. It is not known if an immunosuppressive treatment-as a casual therapy-leads to arrhythmia suppression. In the present study, 12 patients (four female, eight male, mean age 53 +/- 15 years) with a mean left-ventricular ejection fraction of 52 +/- 19% were included. After exclusion of coronary macroangiopathy, the presence of chronic myocarditis was demonstrated by immunohistological evaluation of right-ventricular biopsies taking the number of specific lymphocytes (CD 2-8), of activated macrophages and the degree of HLA-expression on interstitial and endothelial cells as a basis. Seven patients had a successful resuscitation due to ventricular fibrillation in their case history, three patients presented sustained monomorphic ventricular tachycardia and two syncopes with inducible tachyarrhythmias. As a "conventional" therapy ten patients received antiarrhythmic drugs and four patients an implantable cardioverter/defibrillator. After confirmation of the diagnosis by a second biopsy after 3 months, all patients underwent an immunosuppressive therapy with methylprednisolone. The initial dose of 1 mg/kg body weight was reduced by 20 mg each every 2 weeks, until a maintenance dosage of 8-12 mg/day was achieved. If the control study after 6 months still gave a positive result, a combined therapy with azathioprine, 100-150 mg/day, was carried out for a further 6 months. In nine patients (75%), the control biopsy became negative, in three patients (25%), the biopsy remained to be positive. In the group presenting negative biopsies, no tachyarrhythmia relapse occurred within a follow-up period of 49 +/- 13 months, while in the group with positive biopsies, relapses occurred in two of three patients. Complete suppression during EPS after therapy was achieved in 50% of the patients who were inducible before therapy. In addition to lymphocyte infiltration, particularly HLA expression on endothelial and interstitial cells was significantly reduced; left-ventricular ejection fraction was improved only in tendency, while left-ventricular filling pressure decreased significantly. In summary, in patients with chronic myocarditis and malignant ventricular arrhythmias, a high-dose immunosuppressive long-term therapy results in the significant reduction of inflammatory infiltrations in about 75% of the cases and, at the same time, in the effective suppression of arrhythmias.