Four mechanisms that modulate airway smooth muscle function in normal horses were studied in the bronchi of horses affected by the airway obstructive disease heaves. Results were compared with data from historical controls studied by the same personnel in the same laboratory. Rings from the left cranial lobar bronchus (LB1) and small bronchi (5 mm OD) were suspended in muscle baths, and the isometric tension were measured. The inhibitory nonadrenergic noncholinergic (iNANC) function was studied in LB1. After the LB1 segments were pretreated with atropine and contracted with histamine, electrical field stimulation (EFS) induced little or no relaxation, indicating iNANC dysfunction in horses with heaves. Bronchi from animals with heaves were hyporesponsive to EFS and acetylcholine. Epithelial removal augmented the contractile response of small bronchi to acetylcholine more in animals with heaves than in control animals, indicating an enhanced function of epithelial-derived relaxing factor. In contrast, cyclooxygenase inhibition with meclofenamate (10(-6) M) increased the EFS-induced contraction of small bronchi less in affected horses than in control horses, suggesting a change in prostaglandin production in favor of excitatory prostanoids. We conclude that in the bronchi of horses with heaves; the iNANC function is defective, the response of smooth muscle to cholinergic activation is diminished, the production of epithelial-derived relaxing factor is enhanced, and the inhibitory function of prostanoids is reduced.