Human rhinovirus (HRV) infections are associated with exacerbations of asthma and chronic obstructive pulmonary disease that are characterized by a selective neutrophil infiltration. IL-17A, a cytokine derived primarily from activated T cells, has been linked to neutrophilic inflammation of the airways. We hypothesized that IL-17A alters the response of HRV-infected epithelial cells to modulate airway inflammatory cell populations. IL-17A synergistically enhanced HRV-16-induced epithelial production of the neutrophil chemoattractant, IL-8, as well as human beta-defensin-2 (HBD-2), a chemoattractant for immature dendritic cells and memory T cells, but suppressed viral production of the eosinophil chemoattractant, RANTES. These effects were not due to alterations of viral uptake or replication by IL-17A. The synergy between HRV-16 and IL-17A for IL-8 protein production was both dose- and time-dependent. IL-8 induction by IL-17A or HRV-16, alone and in combination, was reduced by inhibitors of the p38 and p44/42 MAPK pathways. By contrast, induction of HBD-2 depended on the activation of the p38 and JNK pathways. The ability of IL-17A to synergistically enhance HRV-induced IL-8 is mediated posttranscriptionally, since IL-8 promoter activation by the combination of the two stimuli was merely additive, whereas the combination of IL-17A and HRV-16 led to stabilization of IL-8 mRNA. Similarly, stimulation of HBD-2 promoter constructs by the combination of IL-17A and HRV-16 was no more than the sum of the individual responses. Further studies are needed to examine HBD-2 mRNA stability. Taken together, these data represent the first demonstration that IL-17A can modify epithelial responses to HRV in a manner that would be expected to favor the recruitment of neutrophils, immature dendritic cells, and memory T cells to the airways.