An enzyme-linked immunosorbent assay was used to measure nasal-wash and serum isotype-specific hemagglutinin antibody responses in 109 seronegative (hemagglutination-inhibiting titer less than or equal to 1:8) adults vaccinated intranasally with live attenuated A/Washington/897/80 (H3N2) or A/California/10/78 (H1N1) cold-adapted (ca) virus or with licensed subvirion vaccine subcutaneously. Live and inactivated virus elicited serum immunoglobulin A (IgA) responses in 83 and 96% of vaccinees, respectively, and elicited serum IgG responses in 72 and 100% of vaccinees. Inactivated virus induced higher titers of serum antibodies than did live virus and stimulated a nasal-wash IgG response more often than did live virus (94 versus 59%, P less than 0.01). In contrast, only 38% of inactivated virus vaccinees had local IgA responses compared with 83% of live virus vaccinees. Serum IgA and IgG and nasal IgG antibody titers remained elevated above prevaccination levels for at least 6 months in most of the live and inactivated vaccine responders, but the mean level of local IgA antibody induced by infection with live virus vaccine, in particular, decreased substantially. Considered in the context of previous work, the finding that live virus vaccine induced relatively long-lasting antibody in both local and serum compartments suggested that this vaccine may be a suitable alternative to inactivated vaccine for use in healthy persons.