BACKGROUND: Bronchiolitis causes substantial disease in young children. Previous findings had indicated that a robust innate immune response was not associated with a poor clinical outcome in bronchiolitis. This study tested the hypothesis that increased concentrations of cytokines and chemokines in nasal wash specimens were associated with decreased severity in bronchiolitis. METHODS: Children <24 months old who presented to the emergency department with signs and symptoms of bronchiolitis were eligible for enrollment. Nasal wash specimens were analyzed for viral pathogens and cytokine/chemokine concentrations. These results were evaluated with regard to disposition. RESULTS: One hundred eleven children with bronchiolitis were enrolled. A viral pathogen was identified in 91.9% of patients (respiratory syncytial virus in 51.4%, human rhinovirus in 11.7%). Higher levels of cytokines and chemokines (interferon [IFN] gamma; interleukin [IL] 4, 15, and 17; CXCL10; and eotaxin) were significantly associated with a decreased risk of hospitalization. IL-17, IL-4, IFN-gamma, and IFN-gamma-inducible protein 10 (CXCL10 or IP-10) remained statistically significant in the multivariate analyses. CONCLUSIONS: The cytokines and chemokines significantly associated with decreased bronchiolitis severity are classified in a wide range of functional groups (T-helper 1 and 2, regulatory, and chemoattractant). The involvement of these functional groups suggest that a broadly overlapping cytokine/chemokine response is required for control of virus-mediated respiratory disease in young children.