A live influenza virus candidate vaccine, "Alice" strain, was evaluated in normal healthy adults. It proved to be safe, with minimal clinical reactions. Thirteen of 21 volunteers (61.9%) with pre-existing titers of hemagglutination-inhibiting antibody of less than or equal to 1:4 and three of nine (33.3%) with initial titers of 1:8-1:16 had four-fold increases in titers of serum antibody. A second dose of vaccine did not increase the frequency or the magnitude of the serum antibody response. Nasal neutralizing antibody responses occurred in six of 18 subjects tested (38.8%). The vaccine virus appeared to produce its effect by replication since vaccine virus was recovered from six of 17 subjects (35%), administration of a vaccine inactivated by ultraviolet irradiation did not produce a response, a 1:10 dilution of virus infected two of five subjects, and a 1:100 dilution infected none of six subjects. The virus was not transmitted to the antibody-negative controls who were confined with infected volunteers. Challenge of 20 volunteers and 26 control subjects with wild-type influenza A/Udorn/307/72 (H3N2) virus revealed a significant reduction in the frequency of infection and illness among subjects who responded to "Alice" vaccine compared with the frequency among unvaccinated controls.