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Serum HAI (hemagglutination inhibition) antibody responses were compared in two groups of 70 age-matched patients (age range, 17 to 82 years) who were vaccinated with bivalent influenza A/New Jersey/76-A/Victoria/75 whole-virus vaccine. The group that was vaccinated intradermally received 40 chick cell-agglutinating units of each viral antigen in 0.1 ml, and the group that was vaccinated subcutaneously received 200 chick cell-agglutinating units of each antigen in 0.5 ml. The serum HAI antibody response to A/New Jersey/76 antigen was significantly higher in the group that was vaccinated subcutaneously; this difference was particularly evident in patients less than or equal to 50 years old. The serologic response to A/Victoria/75 antigen did not differ significantly between the two groups. Levels of antibody before vaccination indicated previous widespread exposure of patients to influenza A/Victoria/75 virus, but not to influenza A/New Jersey/76 virus. Such differences in prior immunologic experience with a particular strain of influenza virus probably determine whether the intradermal route of vaccination is as effective as, or inferior to, the subcutaneous route.