Dendritic cells (DC) can both initiate an immune response and dictate its character. Cytokines are critically involved in this process and, although interleukin (IL)-10 is known as a potent immunosuppressant, the impact of its release from DC remains unclear. Here, we transfer pathogen-conditioned murine DC in vivo and show that, while DC-derived IL-10 can act to limit Th1 development, it is not required for Th2 induction. In both Th2 and Th1 settings, however, IL-10 from cells other than the initiating DC dominates the regulation of the emerging effector cell populations. Surprisingly, the critical source of IL-10 in this process is neither T nor B cells. These data illustrate the distinct actions of IL-10 during differently polarised, pathogen-focussed, DC-driven immune responses in vivo.