A formalin inactivated monkey kidney culture propagated 100-fold concentrated respiratory syncytial (RS) virus vaccine was administered intramuscularly to residents of Harrison and Arthur Cottages in Junior Village, a District of Columbia Welfare Institution for homeless but otherwise normal infants and children. No significant local or systemic vaccine reactions were observed. One to three doses of vaccine were found to produce CF antibody titers of 1:8 to 1:256 in 27 (97%) of 28 seronegarive (<1:4) residents; the vaccine also stimulated high levels of neutralizing antibody. A sharp outbreak of RS virus infection occurred approximately 9 months after the vaccine study was initiated; RS virus was recovered from 60 (41%) of 146 residents and serologic evidence of infection was detected in 37 (92%) of 40 seronegative individuals. Recovery of RS virus was found to be significantly associated not only with the onset of febrile illness but also with the onset of febrile pneumonia illness. The vaccine not only failed to offer protection but also induced an exaggerated, altered clinical response to naturally occurring RS virus infection in the younger vaccinees as 9 (69%) of 13 vaccinated and only 4 (9%) of 47 nonvaccinated Harrison Cottage residents 6–23 months of age developed pneumonia (p< .0001). The paradoxical effect of vaccination suggests that serum antibody may play an active role in the pathogenesis of RS virus disease.