The group B coxsackieviruses are single-stranded RNA viruses that have been implicated in viral myocarditis. Viral infection of the myocardium, as well as the associated inflammatory response are important determinants of the virus-associated myocardial damage. Although these viruses are known as cytopathic viruses that cause death of the host cell, their viral RNA has been shown to persist in cardiac muscle contributing to a chronic inflammatory cardiomyopathy. Thus, it is essential that we understand the mechanism by which Coxasckie B viruses (CBVs) trigger this inflammatory response. In this study we investigated the involvement of Toll-like receptors (TLRs) in the recognition of CBV virions as well as CBV single-stranded RNA. Here we report that the CBV-induced inflammatory response is mediated through TLR8 and to a lesser extent through TLR7.