The efficacy of live attenuated cold-adapted (ca) reassortant influenza A H3N2 and H1N1 virus vaccines against experimental challenge with homologous wild-type virus 7 months after vaccination was compared with that of licensed inactivated virus vaccine in 106 seronegative (hemagglutination-inhibiting antibody titer less than or equal to 1:8) college students. The live attenuated virus vaccines induced as much resistance against illness as did the inactivated vaccine. Vaccine efficacy, measured by reduction in febrile or systemic illness in vaccines, compared with that in controls was 100% for ca H3N2 vaccine, 84% for inactivated H3N2 vaccine, 79% for ca H1N1 vaccine, and 67% for inactivated H1N1 vaccine. Less protection was conferred against upper respiratory tract illness; there was 50 and 77% protection in ca and inactivated H3N2 vaccines, respectively, but there was no protection in ca or inactivated H1N1 vaccinees. The duration, but not the magnitude, of H1N1 wild-type virus shedding in both ca and inactivated vaccinees was significantly reduced compared with controls. In contrast, a significant reduction in the duration and magnitude of H3N2 virus shedding was observed in ca vaccinees but not in inactivated vaccines. After wild-type virus challenge, live ca virus vaccinees demonstrated resistance at least as great 7 months postvaccination as did inactivated virus vaccinees. These observations indicate that live virus vaccines may be a satisfactory alternative to inactivated vaccines for healthy persons.