CRTh2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) is a marker for Th2 cells and activation through CRTh2 stimulates expression of cytokines that are important for allergic responses such as IL-4, IL-5 and IL-13. We have observed CRTh2+ T cells express the IL-25 receptor (IL-25R). IL-25 is produced by the epithelium in response to allergens, parasites, and viruses. We hypothesized IL-25 would modulate acquisition of the Th2 phenotype. The effect of IL-25 on Th2 differentiation was investigated by culturing naive human CD4 T cells in the presence or absence of IL-25. IL-25 alone induced expression of IL-4, GATA3 and CRTh2. Head to head comparison with the canonical Th2 cytokine, IL-4, showed that IL-25 was equally effective in inducing IL-4 expression. These findings suggest IL-25 initiates Th2 differentiation and amplifies production of Th2 cytokines. Consequently, IL-25 inducing pathogens such as RSV may play a role in initiating and exacerbating allergic diseases.