ABSTRACT S-Nitrosothiols(AS-NO) relax tracheal smooth muscle from a variety of animal species, and may have physiological relevance. We therefore studied their effects on human bronchial smooth muscle. S-Nitroso adducts of glutathione, cysteine, N-acetylcysteine and bovine serum albumin relaxed tissues contracted with methacholine with mean ICso±SEM of 3.3 (±1 4), 22 (±45), 25 (±22) and 36 (±7.1) respectively; they were more potent as inhibitory agonists than the corresponding reduced thiol, NaNO2, 01’theophylline, but less potent than isoproterenol(P<. 001). Despite large differences in their molecular weights and dissociation kinetics, the lCso of these AS-NO did not differ significantly from one another, from nitric oxide(NO.) or from sodium nitroprusside. Consistent with the role of cyclic GMP (cGMP) in mediating relaxation responses, S-nitroso-N-acetyl cysteine (S-NO-AC)(1 00 M) increased tissue CGMP levels 4-fold, and 8-bromo-cGMP caused modest tissue relaxation which was potentiated by the phosphodiesterase inhibitor, dipyri-damole (1 SM). However, the guanylyl cydase inhibitors, meth-ylene blue (1 00 M) and LY 83583 (50 SM), failed to modify the relaxation response to S-NO-AC(sodium nitroprusside and