A large number of dendritic cell (DC) subsets have now been identified based on the expression of a distinct array of surface markers as well as differences in functional capabilities. More recently, the concept of unique subsets has been extended to the lung, although the functional capabilities of these subsets are only beginning to be explored. Of particular interest are respiratory DCs that express CD103. These cells line the airway and act as sentinels for pathogens that enter the lung, migrating to the draining lymph node, where they add to the already complex array of DC subsets present at this site. Here we assessed the contributions of these individual populations to the generation of a CD8(+) T-cell response following respiratory infection with poxvirus. We found that CD103(+) DCs were the most effective antigen-presenting cells (APC) for naive CD8(+) T-cell activation. Surprisingly, we found no evidence that lymph node-resident or parenchymal DCs could prime virus-specific cells. The increased efficacy of CD103(+) DCs was associated with the increased presence of viral antigen as well as high levels of maturation markers. Within the CD103(+) DCs, we observed a population that expressed CD8alpha. Interestingly, cells bearing CD8alpha were less competent for T-cell activation than their CD8alpha(-) counterparts. These data show that lung-migrating CD103(+) DCs are the major contributors to CD8(+) T-cell activation following poxvirus infection. However, the functional capabilities of cells within this population differ with the expression of CD8, suggesting that CD103(+) cells may be divided further into distinct subsets.