The efficacy of the synthetic nucleoside ribavirin in the therapy of experimental myocarditis caused by coxsackievirus B3and its effects on peripheral and splenic lymphocyte subsets were investigated. Two week old male C3H/He mice were inoculated with coxsackievirus B3. Ribavirin was administered subcutaneously on days 0 to 15 (experiment I) and on days 4 to 15 (experiment II) in a dose of 200 (experiment I: Group 2, n = 10; experiment II: Group 5, n = 10) or 400 mg/kg per day (experiment I: Group 3, n = 10; experiment II: Group 6, n = 10). Control mice (experiment I: Group 1, n = 15; experiment II: Group 4, n = 14) received an injection of saline solution.In experiment I, mice treated with ribavirin survived significantly longer than did control mice (p = 0.005, Group 1 versus Group 2; p = 0.001, Group 1 versus Group 3). In experiment II, the survival rate on day 15 in ribavirin-treated mice was high compared with that in control mice (Group 4 = 14.3%, Group 5 = 20%, Group 6 = 50%). Myocardial viral titers on days 5 to 8 were significantly lower in ribavirin-treated mice of both experiments than in control mice. Histologic examination showed extensive myocardial necrosis and cellular infiltration in untreated groups; there was less infiltration in Group 3 (p < 0.001) and Group 6 (p < 0.05), less severe necrosis in Groups 2 and 3 (p < 0.001) and Group 6 (p < 0.01) and less calcification in Groups 2 and 3 (p < 0.001) and Groups 5 (p < 0.05) and 6 (p < 0.001).For analysis of lymphocyte subsets of the peripheral blood and spleen, six additional mice from each of the five groups (Groups 1, 2, 3, 5 and 6) were killed on days 6 to 10. The percentages of B cells, Thy 1.2+(pan T), Lyt l+, 23+(precursor of other T cell subsets), Lyt 1+, 23−(helper/ inducer T), Lyt 1−, 23+(suppressor/cytotoxic T and L3T4+(activated helper T) subsets were calculated. In Group 1 (infected, nontreated), the percentages of Thy 1.2+, Lyt 1+, 23+, Lyt 1+, 23−and L3T4+subsets in the peripheral blood and spleen were decreased significantly compared with those of uninfected mice. However, in the peripheral blood of ribavirin-treated mice, the decrease of percentages of Thy 1.2+and L3T4+subsets was significantly less severe than that in untreated mice (Group 1).Thus, early administration of ribavirin effectively inhibited myocardial coxsackievirus B3replication and reduced myocardial damage during the acute viral infection, with improvement of the depletion of pan T and helper T subsets caused by coxsackievirus B3in this animal model.