Enhancement of in vivo antiviral activity of 5, 7, 4'-trihydroxy-8-methoxyflavone (F36) against H3N2 subtype of influenza A virus by drug delivery system (DDS) with hydroxypropyl cellulose (HPC) was studied.Although in the absence of HPC F36 (0.5 mg/kg) showed no antiviral activity against mouse-adapted influenza virus A/Guizhou/54/89 (H3N2) in mice, when F36 solution containing HPC was administered intranasally 5 min after the virus inoculation, proliferation of the virus in both nasal and broncho-alveolar cavities was inhibited significantly.The relationship between concentration (0.2-0.5%) and deposition ratio of HPC was studied. When 10 μl of fluorescein isothiocyanate (FITC)-conjugated HPC solution was administered intranasally to BALB/c mine, deposition ratio of HPC at 6 h after inoculation in nasal cavity was dependent on its concentration. The deposition ratio of HPC in broncho-alveolar cavity, however, was reversely dependent on its concentration.Anti-influenza virus activity of F36 in nasal and broncho-alveolar cavities was dependent both on the concentration and deposition ratio of HPC. HPC was most effective at 0.5% in nasal cavity and at 0.3% in broncho-alveolar cavity. These results indicate that DDS with HPC enhances the anti-influenza virus activity of F36 in vivo.