1 The endogenous cannabinoid agonist, anandamide produced a modest contractile response in guinea-pig isolated bronchus compared with the vanilloid receptor agonist capsaicin. The contractile response to both anandamide and capsaicin was inhibited by the vanilloid receptor antagonist, capsazepine. Furthermore, the NK 2 -selective antagonist, SR48968 but not the NK 1 -selective antagonist, SR140333 inhibited contractile responses to anandamide. 2 The contractile response to anandamide was abolished in tissues desensitized by capsaicin. However, anandamide failed to cross-desensitize the contractile response to capsaicin. 3 The contractile response to anandamide was not signi®cantly altered in the presence of the CB 1 receptor antagonist, SR141716A, nor the amidase inhibitor, phenylmethylsulphonyl¯uoride (PMSF) but was signi®cantly increased in the presence of the neutral endopeptidase inhibitor, thiorphan. 4 The cannabinoid agonist, CP55,940 failed to signi®cantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) response in guinea-pig airways. In contrast, the ORL 1 receptor agonist, nociceptin, signi®cantly inhibited this response. 5 The results demonstrate that anandamide induces a modest contractile response in guinea-pig isolated bronchus that is dependent upon the activation of vanilloid receptors on airway sensory nerves. However, cannabinoid receptors do not appear to play a role in this regard, nor in regulating the release of neuropeptides from airway sensory nerves under physiological conditions.