The initiation of cytotoxic immune responses requires the direct interaction between naive CD8⁺ T lymphocytes and dendritic cells (DCs). Multiphoton imaging in intact lymph nodes (LNs) showed that during priming, naive T cells and DCs establish sequentially brief (i.e., minutes) and long (hours) antigen-specific contacts. We show here that the expression of the Intercellular Adhesion Molecule-1 (ICAM-1) by mature DCs is critical for long-lasting contacts with CD8⁺ T cells but dispensable for short-lived antigen-specific interactions. Serial brief DC-T cell contacts induced early CD8⁺ T cell activation, proliferation, and differentiation into effector cytotoxic T lymphocytes in the first few days after immunization. ICAM-1-deficient mature DCs, however, failed to induce fully effective priming, because CD8⁺ T cells produced reduced amounts of interferon γ and were clonally depleted after 2 weeks. In addition, Icam1^−/− mice failed to respond to rechallenge. We conclude that ICAM-1-dependent long-lasting interactions between mature DCs and naive CD8⁺ T cells determine the survival of activated CD8⁺ T cells and the establishment of effective memory.