The role of tumour necrosis factor (TNF)‐α in the mobilization and migration of human epidermal Langerhans cells (LC) has been investigated. Intradermal injection of normal human volunteers with homologous recombinant TNF‐α was found to cause a dose‐dependent reduction in the frequency of LC within epidermal sheets 2 h later. Equivalent results were obtained when epidermal LC were identified on the basis of either CD1a or HLA‐DR expression. At the dose of TNF‐α used routinely (500 U), treatment resulted in an average reduction in LC density of approximately 24%. Treatment with TNF‐α was associated with a perivascular polymorphonuclear infiltration at 2 h, but the epidermis appeared normal with neither fibrinoid necrosis nor vasculitis, and LC morphology was not affected significantly. These results demonstrate that TNF‐α provides an important signal for LC migration in humans and is likely therefore to play a crucial part in the induction of cutaneous immune responses.