The capacity to migrate from peripheral tissues, where antigen is encountered to lymphoid organs, where the primary immune response is initiated is crucial for the immunogenic function of dendritic cells (DC) . The skin is an accessible and suitable tissue to study migration. Using an organ culture model with human split-thickness skin I addressed the following questions: (1) Do DC leave the epidermis during culture? (2) Do they accumulate in and migrate through dermal lymphatic vessels? (3) Is the human skin organ culture model useful for studies of the initiation and regulation of DC migration? Applying immunohistochemical methods and electronmicroscopy I made the following observations. (1) Spontaneous emigration of Langerhans cells took place in skin cultured for 1-2 days. (2) These cells accumulated within the dermis in string-like non random patterns ('cords'). (3) Ultrastructurally, the cells corresponded to mature DC and electronmicroscopy proved that the accumulations were located within dermal lymphatic vessels. (4) TNF alpha seemed tobe crucial in the initiation of DC migration, whereas GM-CSF and IL-1 had no substantial effect. (5) To detect expected changes in the expression of several costimulatory or adhesion molecules, immunohistochemistry turned out to be not enough sensitive. I conclude that this organ culture model may prove helpful in resolving pathways and mechanisms of DC migration.