In murine skin organ cultures migrating dendritic cells (DCs) have been shown to accumulate in the dermis in a distinct, string-like pattern ( cords ). Electron microscopy proved that these cords represented lymphatic vessels. We wondered whether human cutaneous DCs would follow the same route of emigration. To this end, organ cultures of human skin were set up. Epidermal sheets and tangential thick sections of whole skin were studied.Over three days of culture the density of Langerhans cells (i.e. MHC class II+ cells) in epidermal sheets dropped to 30-50% of the starting values. On sections immunostained with mAb LAG , specific for Birbeck granules, we consistently observed accumulations of LAG+ cells. They were arranged in a non-random, string-like fashion. Double-labeling experiments showed that these cells were strongly MHC class II+ and thus qualified as Langerhans cells. They were not contained in blood vessels (identified with mAb PAL-E). Ultrastructurally these cells exhibited all features of mature DCs. They were located in wide lymphatic vessels that were separated from the surrounding dermal tissue by a thin layer of endothelium, typically devoid of a basement membrane.We conclude, that human cutaneous DCs leave the skin via lymphatic vessels both in vivo and in the in vitro culture system described here. This model may therefore prove useful for the investigation of mechanisms of DC migration in human skin.