The relative contributions of basophils and dendritic cells in Th2 skewing to foreign antigen exposure remain unclear. Here we report the ability of basophils to induce Th2 polarization upon epicutaneous sensitization with different antigens using basophil conditionally depleted Bas TRECK transgenic mice. Basophils are responsible for Th2 skewing to haptens and peptide antigens, but not protein antigens in vivo. Consistent with this, basophils cannot take up or process ovalbumin protein in significant quantities, but present ovalbumin peptide to T cells for Th2 differentiation via major histocompatibility complex class II. Intriguingly, basophils promote Th2 skewing upon ovalbumin protein exposure in the presence of dendritic cells. Taken together, our results suggest that basophils alone are able to induce Th2 skewing with haptens and peptide antigens but require dendritic cells for the induction of Th2 for protein antigens upon epicutaneous immunization.