Muramyl dipeptide (MDP), murabutide (a derivative of MDP), mouse alpha-interferon (MoIFN), and polyinosinic-polycytodylic acid (poly (I-C) were tested in a mouse-influenza virus model for anti-influenza virus activity. None of these compounds administered alone prior to virus challenge had more than minimal ability to protect mice from influenza virus infection. In contrast, mice given either MDP or murabutide 2 days prior to challenge with influenza A/Hong Kong/68 virus and poly I-C 1 day prior to virus challenge had significantly reduced pulmonary virus titers and mortality compared to comparably challenged control mice. No significant reductions in pulmonary virus titers or mortality were seen if MoIFN was given in place of poly I-C in this sequence.