The effect of human recombinant stem cell factor (SCF) on inflammatory mediator release and smooth muscle contraction was evaluated in human isolated intralobar bronchi. Bronchi from 21 of 26 donors contracted in response to SCF. The threshold concentration was approximately 0.01 micrograms/ml. At 1 micrograms/ml, the tissues contracted to about 60% of the carbamylcholine-induced maximum contraction. The responses to SCF mimicked those obtained with anti-IgE. Thus, the contractions to SCF and anti-IgE were inhibited to a similar extent by a combination of a cysteinyl-leukotriene receptor antagonist and a histamine H1 receptor antagonist. SCF also mimicked the effect of anti-IgE in releasing histamine, i-LTD4, and PGD2 from the bronchi. At a threshold concentration for contraction (0.01 micrograms/ml), SCF had no effect on subsequent responses to anti-IgE in the bronchi. The data suggest that human recombinant SCF contracts airway smooth muscle by stimulating the release of contractile mediators from bronchial mast cells. The data fail to support the hypothesis that SCF primes bronchial mast cells to subsequent immunologic stimuli.