Aerosols of double-stranded complexes of polyinosinic and polycytidylic acids (poly I:C) were useful in protecting mice infected with aerosols of influenza (A(2)/Taiwan/64) and parainfluenza type 1 (Sendai) viruses. Administration of poly I:C as an aerosol offers an advantage, particularly in therapy, by eliminating the risk of pulmonary dissemination of viral infections due to intranasally instilled fluids. Treatment of mice with aerosols of poly I:C reduced the infection rate with influenza virus but did not inhibit virus multiplication in the lungs of most of those animals where infection became established. Sendai virus infection rates were undiminished in mice treated with poly I:C, but lung-virus titers were significantly suppressed as compared with those of untreated animals. The maximum poly I:C doses (40 mug) administered by aerosol produced no evidence of toxicity in the mice.