Abnormal endothelin-1 (ET-1) expression has been observed in bronchial asthma and systemic sclerosis with lung involvement. The purpose of this study was to analyze the synthesis of ET-1 in human airway epithelial cells and macrophages under basal conditions and after challenge with tumor necrosis factor-alpha (TNF alpha) or with the glucocorticoid dexamethasone. The ET-1 mRNA level and peptide release were measured in the broncho-epithelial cells BEAS-2B and the monocytic cell line U937. At baseline, U937 cells released low amounts of ET-1 peptide, whereas ET-1 was not detectable in BEAS-2B cells. After TNF alpha treatment, BEAS-2B cells, but not U937 cells, showed a significant increase in ET-1 expression, both at the mRNA and peptide levels. In contrast, dexamethasone elicited an increased amount of ET-1 peptide in U937 medium, but not in BEAS-2B cells. In this latter cell line, dexamethasone pretreatment was unable to inhibit the TNF alpha-induced expression. We conclude that response to TNF alpha and glucocorticoids is cell-type specific with respect to ET-1 production. The response of lung tissue to these agents in vivo is likely to be the overall balance of induction and inhibition in local microenvironments.