Samples of nasopharyngeal secretions from a group of 73 infants with bronchiolitis or upper respiratory illness alone during infection with respiratory syncytial virus were analyzed for leukotriene C4(LTC4) content using a reverse-phase high-pressure liquid chromatography assay with confirmation by radioimmunoassay. Titers of respiratory syncytial virus (RSV)-specific IgE in nasopharyngeal secretion (NPS) specimens were determined using an enzyme-linked immunosorbent assay. The highest concentrations of LTC4were found in the first 3 to 8 days after the onset of illness, and LTC4was detectable in progressively lower concentrations in samples obtained up to 28 days after the onset of illness. LTC4was detected in samples of NPS obtained in the acute phase of illness from 67% of infants with bronchiolitis due to RSV and in 33% of samples of NPS obtained during the same interval from infants with upper respiratory illness alone (p< 0.025). Concentrations of LTC4in children with bronchiolitis were 5-fold higher (1271 pg/ml) then the mean concentration of LTC4in children with upper respiratory illness (224 pg/ml,p< 0.02). LTC4was detected in 83% of the children developing an RSV-IgE response and in 24% of subjects not developing an RSV-IgE response (p< 0.001). Quantities of LTC4measured in NPS were directly correlated with the magnitude of the RSV-IgE response in secretions (r= 0.33,p< 0.02). These studies lend support to previous investigations suggesting that severe bronchiolitis due to RSV results from IgE-mediated hypersensitivity reactions to viral antigens, with release of chemical mediators of airway obstruction. Their implications should be considered in new approaches to therapy of RSV bronchiolitis. (Pediatr Res24: 504–507, 1988)