Plasmacytoid dendritic cells (PDCs) play a pivotal role as cytokine-secreting accessory cells in the antimicrobial immune defense. In contrast, the capacity of PDCs to act as antigen-presenting cells in naive T cell priming remains unclear. By studying T cell responses in mice that lack conventional DCs (cDCs), and by the use of a PDC-specific antigen-targeting strategy, we show that PDCs can initiate productive naive CD4(+) T cell responses in lymph nodes, but not in the spleen. PDC-triggered CD4(+) T cell responses differed from cDC-driven responses in that they were not associated with concomitant CD8(+) T cell priming. Our results establish PDCs as a bona fide DC subset that initiates unique CD4(+) Th cell-dominated primary immune responses.