Present clinical studies of active immunotherapy for malignancies using dendritic cells (DCs) require elucidation of the sites where DCs localize after injection. We evaluated the pattern of distribution of in vitro-generated, antigen-loaded, human DCs labeled with indium-111 oxyquinoline after i.v., s.c., and intradermal injection. Whereas the DCs injected i.v. localized in the lungs and then redistributed to the liver, spleen, and bone marrow, they were not detected in lymph nodes or tumors. A small percentage of DCs injected intradermally migrated rapidly to the regional lymphatics in some individuals. No lymph node activity was detected after s.c. injection. Our results demonstrate that DC distribution to sites of lymphoid tissue is dramatically affected by the mode of administration.