The safety and immunogenicity of a new cold-adapted reassortant influenza B/Yamagata/10/88 virus vaccine was evaluated in healthy young adults with low levels of preinoculation serum antibody to the vaccine virus, and symptoms and viral shedding after vaccination were compared with those following administration of the homologous B/Yamagata/88 wild-type virus. Administration of the cold-adapted virus was well tolerated and resulted in a significantly lower frequency of respiratory symptoms and viral shedding than did the wild-type virus. Twelve of 14 subjects who received the cold-adapted virus had an antibody response to the vaccine virus following vaccination. These data suggest that the B/Yamagata/88 virus is safe and immunogenic in seronegative adults and support the concept that the attenuation phenotype can be transferred reliably and reproducibly to successive new influenza B wild-type viruses along with the six internal gene segments of the cold-adapted influenza B/Ann Arbor/1/66 master vaccine virus.