The objective of the study was to investigate the effect of endothelin-1 (ET-1) on KCl-induced contractions. Tracheal strips were obtained from 12 male rabbits, perfused with Krebs solution and aerated continuously by bubbling with a mixture of 95% O(2)-5% CO(2). Increasing concentrations of ET-1 (10(-12)-10(-7) M) additionally to KCl caused more contractions than KCl-induced (P<0.05). A total of 10(-7) M ET-1-induced 14.56% more contraction. Methylene blue (10(-5) M) decreased all the contractions induced from simultaneous use of KCl and ET-1. Methylene blue caused about 18% relaxation of contraction induced from KCl (80 mM) and ET-1 (10(-8) M). Consequently ET-1 increases the KCl-induced contractions of airway smooth muscles. This effect seem to mediate by a nitric oxide (NO)-guanylate cyclase-cGMP pathway, in which methylene blue is inactivator of guanylate cyclase.