Three injections of an aqueous trivalent parainfluenza virus vaccine failed to provide significant protection against natural disease caused by the parainfluenza viruses. The vaccine stimulated fourfold or greater rises in serum HAI antibody in almost all seronegative recipients. Geometric mean titers following immunization were lower than titers usually observed after natural infection. Respiratory tract antibody was not studied. All recipients of three injections of an inactivated respiratory syncytial virus vaccine who were initially seronegative developed fourfold or greater rises in serum CF antibody. Only 47% showed significant rises in neutralizing antibody. With exposure to natural infection, an unexpected increased incidence of RS virus illness requiring hospitalization among vaccinees was observed as compared to control groups. This difference was most significant in the 6–11 month old group, the youngest group immunized, where 13.7% were hospitalized with RSV illness as compared to only 0.86% of an age-matched unimmunized control group. Four vaccinees had severe bronchiolitis-pneumonia. One vaccinee required prolonged assisted ventilation. It is suggested that some form of altered reactivity exists in the RSV vaccinee, possibly delayed hypersensitivity, which results in more severe illness upon natural exposure. The parallelism in experience between recipients of killed RS and measles virus vaccines is emphasized.