The CD27/CD70‐interaction has been shown to provide a costimulatory and survival signal for T cells in vitro and in vivo. Recently, CD70 expression by DC was found to be important for the priming of CD8⁺ T cells. We show here that blocking CD70 interactions has a significant impact on priming of CD8⁺ T cell responses by vaccinia virus (VV), Listeria monocytogenes and vesicular stomatitis virus (VSV) in mice. However, the priming of specific CD8⁺ T cells upon infection with lymphocytic choriomeningitis virus (LCMV) was only marginally reduced by CD70‐blockade. Blocking of CD70 prevented CD8⁺ T cell priming in DIETER mice, a model in which presentation of LCMV‐derived epitopes can be induced selectively in dendritic cells (DC). In contrast, CD70‐CD27 interactions were not important for the priming of VSV‐specific CD4⁺ T cells or class switch of neutralizing antibodies. As we show that priming of CD8⁺ T cells by the pathogens used here is dependent on antigen presentation by DC and that infection results in up‐regulation of CD70 on DC, we conclude that CD70 expression on DC plays an important role in the priming of CD8⁺ T cells by pathogens. Moreover, the lack of CD70 cannot be completely compensated for by other costimulatory molecules.