Vascular smooth muscle cells in culture are capable of secreting endothelin which is a vasoconstrictor and mitogenic peptide. The effect of glucocorticoids on endothelin release from vascular smooth muscle cells of the rat and rabbit aortas was investigated. Micromolar concentrations of dexamethasone and cortisol caused a 2 to 5-fold increase in endothelin release from the two smooth muscle cell types but no such response was observed in endothelial cells of the bovine aorta. Glucocorticoids appear to selectively induce endothelin release from vascular smooth muscle cells and this may be relevant to glucocorticoid-induced hypertension.