Two live, attenuated, intranasally administered influenza virus vaccines were evaluated in 21 seronegative young children at Vanderbilt Children's Hospital (Nashville, Tennessee). The vaccines were derivatives of a cold-adapted master strain, influenza A/Ann Arbor/6/60 virus, containing the hemagglutinin and neuraminidase of one of two contemporary strains, influenza A/Hong Kong/123/77 (H1N1) or A/Alaska/6/77 (H3N2) virus. Both vaccine strains replicated in seronegative young children without evidence of genetic instability. In addition, both vaccine strains caused no identifiable clinical reactions, were not transmitted to other seronegative children, and gave long-lasting immunity. In a subsequent naturally occurring epidemic of influenza A/Bangkok (H3N2) virus, children previously vaccinated with the related strain, influenza A/Alaska (H3N2) virus, were significantly protected as judged by serologic evidence of reinfection.