Objective: Apply transthoracic Doppler echocardiography (TTDE) in mice to study coronary flow reserve (CFR), an index of coronary microvascular function, in mild and severe forms of experimental viral myocarditis. Methods: BALB/c mice were infected with cardiotropic coxsackieviruses causing either a mild (Nancy-strain) or a severe (Woodruff-strain) myocarditis. Left ventricular dimensions, fractional shortening and CFR (ratio of left coronary artery flow velocity during maximal adenosine-induced vasodilatation to rest) were measured by TTDE before infection and again 1 or 2 weeks after infection. Results: Resting flow velocity did not change after infection. In contrast, CFR reduced significantly 1 week after infection with either virus variant (from 2.5 ± 0.3 to 1.4 ± 0.1 in severe and from 2.4 ± 0.4 to 2.1 ± 0.3 in mild myocarditis) being significantly lower in the severe than mild myocarditis. CFR remained low in severe myocarditis 2 weeks after infection. Fractional shortening decreased to the same levels 1 week after infection with either virus variant (from 0.54 ± 0.02 to 0.43 ± 0.03 in severe and from 0.51 ± 0.03 to 0.44 ± 0.02 in mild myocarditis, p < 0.05). However, 2 weeks after infection mice with severe myocarditis had enlarged left ventricles and lower fractional shortening (0.31 ± 0.03) than mice with mild myocarditis (0.47 ± 0.02, p < 0.01). Conclusions: CFR measured with TTDE is reduced in coxsackievirus myocarditis in mice. Low CFR is associated with progressive heart failure indicating that dysfunction of coronary microcirculation is a determinant of poor outcome in viral myocarditis.