Humoral immunity protects against severe respiratory syncytial virus (RSV) disease, but the range and magnitude of antibody responses in RSV-naive children after RSV infection have not been completely defined. We evaluated RSV-neutralizing antibody and immunoglobulin G responses to RSV F and G glycoproteins in 65 RSV-naive Navajo and White Mountain Apache children aged 0–24 months who were hospitalized with RSV infection. In these children, antibody responses developed against RSV F and G and the central conserved region of RSV G. Twenty-seven of 41 infants <6 months old developed reciprocal log2RSV neutralizing antibody titers ⩾8.0, which correlate with protection of the lower respiratory tract. Multivariate analysis demonstrated that the level of preexisting neutralizing antibody at infection, not age, was the most important factor influencing this response. RSV can induce substantial neutralizing antibody responses in young infants when the titer of pre-existing antibodies is low.