Kinins caused graded relaxations in guinea-pig trachea with epithelium under spontaneous or carbachol-induced tone. The order of potency was: [Tyr 8 ]bradykinin > lysyl-bradykinin > bradykinin > methionyl-lysyl-bradykinin. The bradykinin B 1 receptor agonist des-Arg 9 -bradykinin (1 μM) was inactive. Relaxation in response to bradykinin (100 nM) was unaffected by tetrodotoxin (0.3 μM), nicardipine (1 μM), Ca 2 + -free solution without or plus ryanodine (10 μM), propranolol (1 μM), glibenclamide (1 μM), staurosporine (0.3 μM), nickel chloride (100 μM) or [d-p-Cl-Phe 6 ,Leu 1 7 ]VIP (a vasoactive intestinal peptide receptor antagonist, 0.03 μM), but was partially inhibited by apamin (0.3-1 μM). Both HOE 140 (d-Arg-[Hyp 3 ,Thi 5 ,d-Tic 7 ,Oic 8 ]bradykinin) and NPC 17761 (d-Arg 0 [Hyp 3 ,d-Hype E (trans-thiophenyl) 7 ,Oic 8 ]bradykinin) (0.1-1000 nM) caused graded, reversible and selective inhibition of the bradykinin (100 nM) relaxation, with IC 5 0 values of 1.4 and 19.1 nM, respectively. HOE 140 and NPC 17761 (0.1-10 nM) produced a graded shift to the right of the bradykinin concentration-response curves associated with a reduction of the maximum relaxation. The kinin B 1 receptor antagonist, des-Arg 9 -[Leu 8 ]bradykinin (1 μM), was inactive. Thus, bradykinin-induced relaxation in guinea-pig trachea results from activation of bradykinin B 2 receptors and can be antagonized with high affinity in a selective and reversible manner, through noncompetitive mechanism, by both HOE 140 and NPC 17761. In addition, the bradykinin response does not involve neural pathways, extracellular Ca 2 + influx or mobilization of intracellular Ca 2 + stores sensitive to ryanodine, but is modulated by small conductance Ca 2 + -activated K + channels.