Virus-specific nasal immunoglobulin (Ig) A and serum antibody titers in 67 respiratory syncytial virus (RSV)-infected adults were compared with titers in age-matched uninfected control subjects. Control subjects had significantly higher levels of nasal IgA and serum IgG to the RSV F, Ga, and Gb proteins than infected subjects. Serum neutralizing-antibody titers to group A and B RSV strains were also lower in infected subjects, although differences were not as large. Multivariate analysis found that low RSV-specific nasal IgA was an independently significant risk factor for RSV infection.