Eighteen consecutive patients, admitted with a diagnosis of dilated cardiomyopathy (DCM), to the Cardiology Section, Department of Internal Medicine, University Hospital, Uppsala, Sweden were enrolled into the study. All patients suffered signs of cardiac incompensation of variable duration. Patients were defined by conventional clinical investigations including chest X-ray, ultrasound, g-camera, catheterization and endomyocardial biopsy with histological evaluation by a specially trained pathologist. Angiography was performed to exclude ischemic heart disease. Several patients were diagnosed as having a specific reason for the cardiac insufficiency, like pheochromocytoma, SLE, ethylism, ischemic heart disease and hypertrophic cardiomyopathy. In this group all 7/7 had negative serology against Coxsackie B viruses. In the other group of idiopathic CM, no other etiology could be found. Serological analysis in this group showed high IgM titres against Coxsackie viruses in 6/8 patients. EDTA-blood was taken for tissue-typing using DNA probe hybridisation. 6/12 patients had DQB1:4 using the newest nomenclature, vs 17% in the control population. The reversed picture was observed for DQB1:2, occurring in 1/12 patients, vs 19% in the normal population, thus indicating a protective value of this genotype, which to our knowledge has not been described before. The results indicate a dual dependence of (host) genotype and (virus) serotype according to the Doherty-Zinkernagel hypothesis. Thus, it would also be in agreement with the virus-immune hypothesis suggested more than 20 years ago to explain the enigmatic pathogenesis of DCM.