The therapeutic efficacy of an experimental antiviral agent, WIN 54954, was evaluated in murine myocardial infection with coxsackievirus A9 (CVA9). Eight-month-old male Swiss Webster mice were inoculated with 1.5 x 10(4) PFU of CVA9, Boston strain 13. WIN 54954, a broad-spectrum antipicornavirus agent, was administered orally in a dose of 0.25, 2.5, 25, 50, 100, or 200 mg/kg of body weight per day on days 1 to 3 after virus inoculation. Control animals received xanthan gum carrier only. Mice were sacrificed on day 4. Myocardial titers of virus were determined and found to be significantly lower in the four highest dose treatment groups (P less than 0.001 for all groups) compared with controls. Heart weights were also significantly lower compared with controls in these four groups (P less than 0.001 for all groups). When mice received 50 mg of WIN 54954 per kg daily beginning at either 48 or 72 h postinoculation, myocardial titers were once again significantly reduced compared with those of controls (P less than 0.001 for both groups). Neurological toxicity was observed in the 100- and 200-mg/kg/day groups but not in the lower-dose groups. Thus, WIN 54954 effectively reduced myocardial CVA9 replication in a murine model.