In human isolated bronchial preparations, the endothelinB (ETB) receptor-selective agonist, sarafotoxin S6c (Stx6c; 1 nM) increased nerve-mediated contraction in response to electrical field stimulation (EFS) at 0.5-1 Hz from 19 +/- 4% to 42 +/- 7% (n = 9). This effect was blocked in the presence of the ETB receptor-selective antagonist, BQ-788 (10 microM). These data are consistent with findings in some animal species that ET-1 and related peptides have marked neuromodulatory influences on the cholinergic system. Furthermore, they provide additional support for the concept that ET-1 may have a mediator role in bronchial obstruction in asthma.