Mice were vaccinated intranasally (i.n.) or with small-particle aerosols (SPA; 2 mum) or large-particle aerosols (LPA; 8 mum) of an attenuated, temperature-sensitive, recombinant A influenza (H3N2) virus, ts-1 (E). Serum virus-neutralizing and hemagglutination inhibition antibodies were detected for all vaccinated mice by 28 days. Bronchoalveolar wash fluids had increased levels of immunoglobulin (IgG, IgA) only in the i.n. -vaccinated mice. Hemagglutination and virus-neutralizing antibodies were detected in the SPA- and i.n. -vaccinated groups but not in the LPA vaccinates. Upon challenge with SPA of a mouse virulent H3N2 influenza vitus, total protection was obtained for the SPA- and I.N. -vaccinated mice, whereas only 89% of the LPA group survived. Replication of the challenge virus was signifcantly repressed in both the lower and upper respiratory tracts of the three groups of vaccinated mice compared to the nonvaccinated controls. The protection afforded the SPA- and i.n. -vaccinated mice was the same as measured for mice after recovery from earlier subelthal active infection with virulent virus.