Rimantadine HCl was assessed for its effect on influenza A virus titer in lungs of infected BALB/c mice. Rimantadine administered orally via drinking water, with and without an intraperitoneal prophylactic loading dose, was compared to intraperitoneal administration. Mice were infected with a non-lethal dose of influenza A/Port Chalmers/H3N2 virus and the pulmonary virus titers were determined at intervals over a 21 day period. Prophylactic treatment with rimantadine followed by oral administration resulted in up to a 4 log10 reduction in pulmonary virus titer. The oral doses given to the mice were comparable on a mg/kg/day basis to those recommended for treatment of human infections. Reductions in pulmonary virus titers also occurred after intraperitoneal rimantadine treatment which included a prophylactic dose, but the reductions in pulmonary virus titers were less striking and not consistent over the course of infection. There were no significant reductions in pulmonary virus titers by either route if treatment was started 8 h after exposure to virus.