Coxsackievirus B3 (CVB3) is the second main causes of viral myocarditis. Mouse infection with CVB3 mimics the heterotypic response to virus-induced disease observed in humans. Here we have used Evans blue dye as a quantitative biomarker for susceptibility to CVB3-induced myocarditis in addition to histopathological semi quantitative measures. We have found evidence of linkage between susceptibility to viral myocarditis and three loci. A locus on chromosome 1 was linked to sarcolemmal disruption in males (P=0.00005), a second locus on chromosome 4 was also linked to sarcolemmal disruption in males (P=0.0022). A third locus on distal chromosome 3 was linked to myocardial infiltration, with a logarithm of odds (LOD) score of 4.7 (P=0.0045), as well as sarcolemmal disruption in females (P=0.0015). These results provide strong evidence for the presence of loci contributing to the susceptibility of mice to viral myocarditis. Given the complexity of the regulation, development and prognosis of myocarditis the QTLs identified in this study will represent new avenues for developing new therapeutic strategies to control the disease.