The co-ordinate action of several cytokines determines the nature, severity and duration of myocarditis. Interkeukin (IL)-12 mediates a broad range of effects on both innate and acquired immunity. However, thein vivorole of IL-12 in viral myocarditis remains to be elucidated. To clarify the role of IL-12 in viral myocarditis, we treated mice inoculated with the encephalomyocarditis virus (EMCV), with recombinant IL-12 and neutralizing anti-IL-12 antibody. The successive administration of 10 ng of IL-12 from the day of virus inoculation to 5 days thereafter, reduced mortality, myocardial damage and viral replication in the heart tissue. The gene expression of IL-12p35 and IL-12p40 was enhanced in the hearts of EMCV inoculated mice. Treatment with neutralizing anti-IL-12 resulted in increased mortality of mice inoculated with EMCV. In conclusion, endogenous and exogenous IL-12 play protective roles in murine viral myocarditis.