Objective: The aim of this study was to investigate of effects and the possible mechanisms of effects of ketamine on the isolated trachea preparations from control and ovalbumin sensitized guinea pigs. Material and Methods: Adult male guinea pigs were randomly allocated to two experimental groups. We tested the relaxant effects of ketamine (10(-8) M to 3 x 10(-4) M) on the isolated trachea preparations precontracted with carbachol (10(-6) M) in control and ovalbumin-sensitized guinea pigs. We also evaluated the effects of ketamine on the levels of cGMP in isolated tracheal smooth muscle strips with radioimmunoassay. Results: Although ketamine (10(-8) to 3 x 10(-4) M) produced concentration-dependent relaxation on isolated trachea preparations precontracted by carbachol (10(-6) M) in both groups, relaxations in control group were significantly high when compared to ovalbumin-sensitized group (p< 0.05). Preincubation of trachea preparations by indomethacin (10(-5) M) and propranolol (10(-4) M) did not produce a significant alteration on ketamine-induced relaxation responses (p> 0.05), while preincubation by N(w)-nitro L-arginine methyl ester (3 x 10(-5) M) significantly decreased the ketamine-induced relaxation responses in both groups, preincubation by aminoguanidine (3 x 10(-5) M) decreased the ketamine-induced relaxation responses in ova-sensitized group (p< 0.05). Conclusion: Ketamine induced concentration-dependent relaxations in precontracted isolated trachea smooth muscle of guinea pigs in the both groups. These relaxations were independent from cyclooxygenase products released from respiratory epithelium and stimulation of beta adrenergic receptors. The relaxation caused by ketamine seems to be mainly related to the nitric oxide/cGMP pathway, especially eNOS pathway. Although ketamine caused much less relaxation in ova-sensitized group, ketamine can be used as a proper anesthetic agent in patients with airway hyperresponsiveness and bronchial asthma.