During infection, Toll-like receptor agonists induce natural killer (NK)-cell activation by stimulating dendritic cells (DCs) to produce cytokines and transpresent IL-15 to NK cells. Yet the cellular dynamics underlying NK-cell activation by DCs in secondary lymphoid organs are largely unknown. Here, we have visualized NK-cell activation using mice in which NK cells and DCs express different fluorescent proteins. In response to poly I:C or lipopolysaccharide, NK cells maintained a vigorous migratory behavior, establishing multiple short contacts with maturing DCs. Furthermore, mature antigen-loaded DCs that made long-lived interactions with T cells formed short-lived contacts with NK cells. The different behaviors of T cells and NK cells during activation was correlated with distinct calcium responses upon interaction with DCs. That NK cells become activated while remaining motile may constitute an efficient strategy for sampling local concentrations of cytokines around DCs in secondary lymphoid tissues.