Coxsackievirus B (CB) 4 causes transmural myocarditis in suckling mice with ensuing development of focal ventricular thinning or aneurysms. We studied whether subsequent infection with another cardiotropic virus influences the expression of CB4 disease. CB4 infection was established in 2-day-old CD1 mice by intraperitoneal (IP) inoculation. Three weeks later, surviving animals were randomized to receive CB3 or saline IP. They were then killed over a 45-day period. CB4 neutralizing antibody (NA) titres were comparable in both groups (31 +/- 23 vs 37 +/- 19). CB3 NA were detected in CB3 infected animals only (72 +/- 86 versus 0). The incidence of myocarditis was comparable (67.4% vs 55.2%). The indices of histopathological changes (assessed according to a semiquantitative grading scale from 0-4) were greater among CB3 recipients on day 9 post CB3 challenge (1.38 +/- 0.43 vs 0.46 +/- 0.4, P < 0.001) and to a lesser extent, on day 13 (0.56 +/- 0.56 vs 0.19 +/- 0.38, P > 0.1). On days 30, and 45, these indices became similar in both groups. Focal thinning was noted on days 45 in 6/11 animals with CB4 infection alone and in 0/11 mice with subsequent CB3 infection (P = 0.006). These findings show that CB3 myocarditis can be expressed in mice with prior CB4 disease, that sequential infections do not lead to cumulative cardiac injury, and that subsequent CB3 infection suppresses the formation of CB4 induced ventricular aneurysms.