To better understand the duration of immunity against respiratory syncytial virus (RSV) and the role of serum antibodies to the surface glycoproteins, F and G, in susceptibility to reinfection, 15 adults with previous natural RSV infection were challenged with RSV of the same strain group (A) at 2, 4, 8, 14, 20, and 26 months after natural infection. By 2 months about one-half and by 8 months two-thirds of the subjects became reinfected. Each challenge resulted in infection in at least one-fourth of the subjects. Within 26 months 73% had two or more and 47% had three or more infections. The duration of immunity tended to increase after two closely spaced infections. Higher neutralizing, F and GAantibody levels before challenge correlated significantly with protection against infection. However, even in subjects with the highest antibody levels, the risk of reinfection was 25%. Specific nasal 19A antibody titers did not correlate significantly with protection. This suggests that humoral neutralizing, F, and G antibodies correlate with resistance to reinfection, but protection is far from complete and is of short duration.