Recent studies have identified a contiguous network of class II MHC-bearing dendritic cells (DC) in the airway epithelium of several species, including humans. This network seems comparable to the epidermal Langerhans cell population, comprising up to 700 DC per mm2 of airway epithelium. Moreover, it accounts for virtually all local immunostaining for class II MHC, suggesting an important role in surveillance for inhaled Ag. This study examines the turnover of these airway DC using a radiation chimera model that uses congenic rats expressing different allotypic variants of CD45, detectable via mAbs. Steady-state bone marrow renewal of the airway DC population (which is continuously depleted by migration of mature cells to draining lymph nodes) was interrupted via x-irradiation or high-dose dexamethasone, after which the resident population declined by 85% over the ensuing 72 h. After transplantation with congenic bone marrow and an initial lag period for graft establishment, the airway DC population was rapidly restored to preirradiation levels. These findings indicate a half-life of < or = 2 days for airway epithelial DC. In contrast, epidermal Langerhans cell half-life was > or = 15 days. The only comparable (short) half-life previously reported for a peripheral tissue DC population, is that derived from the gut wall. This indicates that rapidly turning over DC populations are a unique feature of the major "mucosal" organ systems, which is consistent with these DC playing an important role in surveillance of mucosal tissues for incoming Ag.