For the 1989-1990 influenza virus vaccine the B component was changed because a new strain, B/Yamagata/16/88, appeared in Southeast Asia. Ferrets infected with B/Yamagata and sheep immunized with B/Yamagata vaccine developed hemagglutination inhibition (HI) antibody responses that were not cross-reactive with other influenza B strains including the predominant strain, B/Victoria/2/87. However, data from healthy adults indicated that a broadly reactive HI antibody response could be expected against earlier influenza B virus strains. In order to determine if the antibody response in children was similarly broadly crossreactive, sera were collected from high-risk children who received the commercial trivalent influenza virus vaccine (which included influenza B/Yamagata/16/88). Sera were tested by hemagglutination inhibition and neutralization for antibodies against B/Yamagata/16/88 and B/Victoria/2/87. Two groups of children were immunized: those with a history of previous influenza virus vaccination and those with no history of prior vaccination for influenza. The latter group was younger (mean age 20 months) than the previously immunized group (mean age 29 months). Seven of the 12 previously immunized children had preexisting antibody against influenza B viruses. Reciprocal geometric mean antibody titers (GMT) for these children increased from approximately 8 to 128 for B/Yamagata and from 16 to 128 for B/Victoria. Three of the 11 children not previously immunized had detectable antibody against influenza B viruses. Excluding those three, the children not previously immunized had increases in GMT from <8 to 128 for B/Yamagata but no change in titer for B/Victoria (pre and post GMT <8). There was an extremely good correlation between HI with detergent disrupted virus and neutralizing antibody titer. For all sera the data suggest that immunologically primed but not unprimed children develop a cross reactive antibody response after immunization with an influenza B virus.