The relationship of serum antibody to respiratory syncytial virus (RSV) and risk of RSV infection was prospectively evaluated in frail elderly persons. Baseline blood samples from 22 subjects who developed symptomatic RSV infection during the 26-month study and from 22 control subjects who did not become infected with RSV were compared. The mean serum IgG titer to RSV fusion protein was significantly lower in the RSV-infected group than in the controls (15.4 +/- 1.6 vs. 16.4 +/- 1.8, P = .05), as were the neutralizing titers to group A RSV (12.4 +/- 2.2 vs. 14.2 +/- 2.2, P = .008) and group B virus (9.1 +/- 2.1, vs. 10.3 +/- 1.5, P = .01). These results suggest that older adults with low titers of serum neutralizing antibody may be at greater risk of developing symptomatic RSV infection than those who have high antibody titers.