The effect of salicylates or indomethacin usage during viral infection was investigated in a murine model of coxsackievirus B3 myocarditis. Eighty-two 3-week-old CD1 mice received 3 x 10(5) median tissue culture infective dose (TCID50) of coxsackievirus B3 intraperitoneally. Then they received salicylates, indomethacin, or saline solution daily for 10 days. Mortality, viral and antibody titers, interferon levels, and pathologic changes in the heart were compared. Mortality (2/33, 4/15, and 0/34, respectively) and virus titers (10(4.72), 10(4.78), and 10(3.4) TCID50, respectively) were higher, interferon levels (300, 267, and 980 IU, respectively) were lower, and pathologic changes were worse in treated animals (antibody titers were similar). These findings indicate that nonsteroidal anti-inflammatory agents adversely affect the course of acute coxsackievirus B3 murine myocarditis. Determination of the pathogenesis of this deleterious effect requires thorough evaluation of virus-host interactions.