The in vitro contractile and relaxant responses of tracheal smooth muscle strips (TSM) and third-generation bronchi (3B) of control horses and horses with recurrent obstructive disease (heaves) were compared. Acetylcholine (ACH) sensitivity of the diseased tissues was less than that of tissues from control horses, especially at the level of the third generation (EC50 controls 15 +/- 11 microM vs 81 +/- 17 microM for heaveys). Despite tracheal and bronchial hyporesponsiveness to ACH, these tissues from heavey horses were hyperresponsive to EFS. The inhibitory effect of isoproterenol and electrical field stimulation (EFS) was examined in histamine-precontracted airways pretreated with atropine (1 microM), indomethacin (3 microM), and phentolamine (1 microM). Precontracted tissues of both groups at both levels of airway demonstrated similar concentration-dependent relaxation in response to cumulative doses of isoproterenol (0.1 nM to 0.1 mM). EFS of precontracted tissues caused 80-90% relaxation in the TSM in both groups and 21% relaxation in 3B of the control group. Electrical field stimulation relaxation of precontracted tissues was not seen in the diseased 3B, suggesting a lack of inhibitory innervation. EFS of similarly precontracted tissues plus propranolol (1 microM) resulted in only 46% relaxation in the TSM of both groups but did not reduce the EFS relaxation of control 3B, suggesting the presence of both sympathetic and nonadrenergic noncholinergic nerves (NANC) in the trachea but only NANC in the 3B.