Adenovirus infection after stem cell transplantation is a significant cause of morbidity and mortality, especially in children. A robust T-cell response induced by dendritic cells (DC) is crucial for clearing the virus, suggesting their pivotal role for the response to human adenoviruses (HAdV). Despite the widespread use of adenoviral vectors, the properties and kinetics of HAdV infection of DC have not been addressed yet. We show that a recent clinical HAdV, subgenus C/serotype 2 (strain BB2000-61), infects cells of the myeloid lineage. Infected DC produce early and late viral antigens and show an altered expression of surface markers. Infection of monocytes renders them refractory to differentiation into DC. Additionally, HAdV-infected DC are strong stimulators of CD8+ T cells. In summary, HAdV seems to manipulate the immune response by infection of DC and possibly uses the infection of monocytes as a means to escape recognition by T cells.