A significant reduction in the death rate of infant mice infected with ten 50% lethal doses (LD50) of coxsackievirus A16 was observed when they were treated 58 h after infection with two injections of guanidine at 145 mg/kg per injection. Tremors occurred at this level but disappeared after treatment was discontinued. Tremors were apparent, but less severe at 97 mg/kg per injection and did not occur at 48 mg/kg per injection. No antiviral effect could be detected at either of these levels of guanidine. When an inactive level of guanidine (97 mg/kg per injection) was combined with 1.7 mg/kg per injection of LY122771-72, LY127123, or 2-(alpha-hydroxybenzyl)benzimidazole (HBB) and 17 mg/kg per injection of 2-guanidino-benzimidazole (GB), significant activity resulted with 2-8 treatments begun 58 h after infection. The same treatment schedule using 136 mg/kg per injection of LY122771-72, 90 mg/kg per injection of LY127123, 136 mg/kg per injection of HBB and 68 mg/kg per injection of GB produced no effect. Guanidine-associated tremors were also enhanced by the addition of the substituted benzimidazoles. When guanidine was reduced to 48 mg/kg per injection, 34 mg/kg per injection of LY122771-72 was required to produce a significant reduction in the death rate and no tremors were observed.