The ability of antigen to contract passively sensitized tissues was examined in human central (5 to 12 mm) and peripheral (0.5 to 2 mm) bronchi. Both central and peripheral bronchi contracted to ragweed antigen E (RW AgE), and these contractions were virtually abolished by a combination of indomethacin, cysteinyl-leukotriene, and histamine antagonists. There were, however, quantitative differences in contractile responses and in mediator release to RW AgE between central and peripheral bronchi. RW AgE was approximately 20-fold more potent in contracting peripheral bronchi compared with central bronchi. On a per weight of tissue basis, RW AgE released six-fold more histamine, 15- to 20-fold more immunoreactive leukotriene D4 (i-LTD4) and two- to 10-fold more prostanoids in the peripheral bronchi compared with central bronchi. Anti-IgE mimicked the effect of RW AgE with respect to inflammatory mediator release and with respect to the magnitude of the contractile response in peripheral and central bronchi. Anti-IgE, however, was more potent in contracting central than peripheral bronchi. Moreover, in peripheral bronchi, contractile responses to anti-IgE were only partially inhibited by a combination of indomethacin, cysteinyl-leukotriene, and histamine antagonists. These results indicate that the qualitative characteristics of antigen-induced mediator release and muscle contraction are similar in central versus peripheral bronchi. However, RW AgE is much more potent in causing smooth muscle constriction, and is capable of releasing a greater quantity of inflammatory mediators in peripheral bronchi/bronchioles than in the more central bronchi.