DT-5461 enhanced host resistance to Sendai virus infection in mice. Intranasal (i.n.) administration of 200 micrograms of DT-5461 per mouse 3 days before infection was the most effective administration route, dose and timing. DT-5461 enhanced the cytotoxicity of murine natural killer (NK) cells. In addition, DT-5461 activated murine peritoneal macrophages, resulted in augmented of cytotoxicity and the induction of tumor necrosis factor-alpha (TNF-alpha). Therefore, these immunomodulating activities presented by DT-5461 caused protection against Sendai virus infection.