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Ribavirin, amantadine, and the two drugs in combination given in small-particle aerosol were highly effective in the treatment of influenza A infection in mice. Treatment was started 72, 96, and 120 h after inoculation and was given continuously for 4 days. With increasing delay in start of treatment, there was a pronounced reduction in effectiveness of ribavirin but not in that of amantadine. The combination treatment reflected the loss of ribavirin activity. Leukocyte infiltration and virus titers in the lungs were inversely related to the effectiveness of treatment. Influenza B infection treated 72 h after inoculation responded only to ribavirin, as indicated by the criteria described for influenza A. Intraperitoneal administration of drug begun 72 h after inoculation in regimens equivalent to aerosol afforded less protection than aerosol treatment.

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