A previously unreported mechanism for the induction of delayed-type hypersensitivity (DTH) was studied in detail. The subcutaneous injection (without adjuvant) of spleen dendritic cells (DC) pulsed with keyhole limpet haemocyanin (KLH) into syngeneic BALB/c mice caused DTH when the ear was later injected with the same antigen. When KLH-pulsed DC were transferred intravenously, DTH was not induced, although the titre of anti-KLH antibodies rose after such transfer. The intravenous transfer of KLH-pulsed DC into mice immunized subcutaneously with KLH in complete Freund's adjuvant (CFA) at the same time (in the sensitization phase), but not when the ear was challenged with KLH (in the effector phase), had a suppressive effect on DTH, in an H-2-restricted way. When radiolabelled DC were transferred intravenously, they migrated into the spleen, but when transferred by subcutaneous injection, they stayed in the skin or migrated into the lymph nodes. In splenectomized mice immunized with KLH, the intravenous transfer of KLH-pulsed DC did not cause production of anti-KLH antibodies and did not suppress DTH. These findings suggest that the anatomical sites in which antigens are presented (i.e. the spleen or lymph nodes) rather than the type of cell that first presents antigens to the immune system governs whether DTH or antibody production is induced. Antibody production was induced when antigens were presented in the spleen.