The pathogenesis of viral myocarditis is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a model of infection with coxsackievirus B3 (CVB3) to characterize the contribution of host genetics to viral myocarditis in mice of different genetic backgrounds but with a common H2 haplotype: A/J and B10.A-H2 a .Here we have used Evans blue dye as a quantitative biomarker for susceptibility to CVB3-induced myocarditis in addition to histopathological semiquantitative measures. We have found evidence of linkage between susceptibility to viral myocarditis and three loci. A locus on chromosome 1 centered on D1Mit200 was linked to sarcolemmal disruption in males (P ¼ 0.00005), a second locus on chromosome 4 centered on D4Mit81 was also linked to sarcolemmal disruption in males (P ¼ 0.0022). A third locus on distal chromosome 3 centered on D3Mit19 was linked to myocardial infiltration, with a logarithm of odds (LOD) score of 4.7 (P ¼ 0.0045), as well as sarcolemmal disruption in females (P ¼ 0.0015). These results provide strong evidence for the presence of loci contributing to the susceptibility of mice to viral myocarditis.