Airway epithelial cells have a potential to produce cytokines which are relevant to airway inflammation. To elucidate the mechanisms of their regulation, we focused on the effects of three chemical mediators [histamine, platelet-activating factor (PAF) and endothelin-1] important in the pathogenesis of bronchial asthma. Histamine, but not PAF or endothelin-1, showed a dose-dependent stimulatory effect on the release of interleukin-6, interleukin-8 and granulocyte-macrophage colony-stimulating factor by normal and transformed human bronchial epithelial cells when studied 6 h after the treatment. The process required protein synthesis as evaluated by the effect of cycloheximide, and was mainly via H1 receptor. We concluded that histamine might be involved in the activation of airway epithelial cells to release inflammatory cytokines in allergic responses.