The effects of the immunosuppressant drug cyclosporine were studied in the murine model of Coxsackie B3 myocarditis. Ten BALB/c mice, given daily cyclosporine (15 mg/kg) intraperitoneally but not infected, were normal in all respects after 2 weeks. All 32 IALB/c mice infected, but given no cyclosporine, survived and had moderate myocardial mononuclear infiltrates and minimal necrosis at 7 and 14 days. In contrast, 24 mice concurrently infected and given cyclosporine had a high mortality rate (75%) and a significantly attenuated mononuclear infiltrate in the presence of enhanced necrosis when compared with control infected mice. Sixteen mice started on the drug 1 week after infection had a lower mortality rate (55%), but very similar histologic abnormalities. In contrast to negligible or no virus in the hearts of infected mice that were not given cyclosporine, drug treated, infected groups had easily detectable virus in their hearts 14 days after infection. An identical study in Swiss ICR mice yielded similar results. Cyclosporine, when given early during acute murine Coxsackie