The immunogenic response of mice vaccinated intranasally or subcutaneously with increasing doses of a purified, concentrated intact A(2)/Taiwan influenza vaccine or its Tween-ether derived vaccines was compared. Immunogenicity was measured by serum neutralization and hemagglutination-inhibition antibodies, lung lesions scores, and protection against respiratory challenge with live airborne influenza virus. Intact (untreated) vaccine, Tween-ether-treated (ET) vaccine, and the isolated hemagglutinins (HA) provided protection and stimulated homologous antibody response at the 35- and 70-chicken cell agglutination (CCA) unit level. At a lower dosage level, the vaccines administered by the subcutaneous route appeared to confer better protection. The ET vaccine was superior to intact virus or HA vaccines when administered subcutaneously. The minimum amount of the HA and intact vaccine given subcutaneously that protected mice against respiratory challenge was 7 CCA units (3.5 units injected twice) compared to 0.7 CCA units (0.35 units injected twice) for the ET vaccine. No heterologous antibody to the A/PR/8/34 or B/Mass/3/66 was noted. Low-level serum-neutralizing antibody was found against the A(2)/Japan/170 strain but, despite high levels of homologous A(2)/Taiwan/64 antibody, no cross-reactivity was found with the recent A(2)/Hong Kong/68 variant.