This study investigated the effects of neurokinin A (NKA) on cholinergic neural responses in human bronchus. NKA (0.1 nM) did not alter the contractile response to submaximal electrical field stimulation. However, K+ channel blockade with 4-aminopyridine (4-AP) (0.1 mM) potentiated the response to electrical field stimulation (to 182 +/- 25% of control, n = 4, P less than 0.05) and subsequent addition of NKA in the presence of 4-AP produced further potentiation (to 123 +/- 6% of the response to 4-AP n = 4, P less than 0.05). Neither 4-AP (0.01 or 0.1 mM) nor NKA in the presence of 4-AP potentiated the actions of exogenous acetylcholine but in these experiments 4-AP itself produced a marked direct contractile response. Thus NKA in the presence of K+ channel blockade potentiates cholinergic neural response in human bronchus and this occurs at a prejunctional site.