The therapeutic efficacy of aerosolized aprotinin, a natural proteinase inhibitor, against influenza and paramyxovirus bronchopneumonia of mice is shown. Small-particle aerosol of aprotinin solution was generated by a Collison type nebulizer and infected mice were exposed to aerosol atmosphere by four 30-40 min incubations per day for 6 days. This regimen provided an inhalation aprotinin dosage of approx. 6 micrograms/mouse/day. With such treatment more than 50% of mice infected with lethal doses of either influenza virus or paramyxovirus were protected from death. A suppression of the development of fatal hemorrhagic bronchopneumonia and a normalization of the body weight gain were observed in infected mice treated with aerosolized aprotinin. These data suggest that low doses of aerosolized proteinase inhibitors could be successfully applied against respiratory influenza-like virus diseases.