The cotton rat model was used to test whether systemically administered immunoglobulin could protect nasal tissues against low challenge doses of respiratory syncytial virus (RSV). Animals were pretreated by intraperitoneal injection of human immunoglobulin with moderate (1:2226) or high (1:15,000) neutralizing antibody titers to RSV (day 0), challenged intranasally with RSV Long at doses ranging from 10(1) to 10(5) pfu (day 1), and sacrificed for virus titration (day 5). Pretreatment with moderate-titer immunoglobulin effected complete or near complete nasal protection against low to moderate (10(1)-10(3) pfu) RSV challenge doses and a significant reduction in nasal RSV titers at high (10(4)-10(5) pfu) challenge doses. Pretreatment with high-titer immunoglobulin effected near complete nasal protection at an RSV challenge dose of 10(3) pfu and highly significant and significant reductions in nasal RSV titers at challenge doses of 10(4) and 10(5) pfu, respectively. Immunoprophylaxis effected complete or near complete pulmonary protection at all RSV challenge doses.