Respiratory syncytial virus (RSV) is a respiratory pathogen that causes significant morbidity in infants and young children. The importance of chemokines during RSV infection for respiratory symptoms has not been fully elucidated. The current study examined the effect of RANTES (CCL5) on airway pathophysiology after RSV infection. BALB/c mice produce RANTES (CCL5) after RSV infection that correlates with the changes in pathophysiology. Animals treated with anti-RANTES (CCL5) antibody demonstrated significant decreases in airway hyperreactivity (AHR). Delayed treatment with anti-RANTES (CCL5) at day 5 of infection also significantly reduced development of AHR on day 9 of infection, suggesting that RANTES (CCL5) may be a target in established disease. Determination of Th1/Th2-associated cytokine patterns indicated that anti-RANTES (CCL5) treatment increased IL-12 production, thus altering the lung environment. The assessment of RANTES (CCL5) production in vitro and in vivo demonstrated that it was regulated by IL-13, a cytokine that is related to RSV-induced AHR in this mouse model. These data show that RANTES (CCL5) is an important mediator of the pathophysiological responses seen in RSV infection.