The site of action of resiniferatoxin(RTX) and capsaicin and the pharmacological consequences of the resultant tachykinin release were examined in the guinea pig trachea. RTX and capswan were both potent and efficacious contractors of isolated tracheal smooth muscle. RTX was about 20-fold more potent than capsaicin, with-log (M) ECro values of 8.88±0.09 (n= 1 4) and 7.55±0.07 (n= 1 4), respectively. The putative capsaicin receptor antagonist capsazepine(1 0 M) effectively inhibited responses to both RTX and capsaicin in a competitive fashion. The-log (M) pl (5 values for capsazepine against resi-niferatoxin and capsaicin were 6.28±0.25 and 6.04±0.13, respectively. Contractile responses to RTX and capsaicin were unaffected by the NK-1 antagonist CP 96345(0.3 SM), partially inhibited by the NK-2 antagonist SR 48968(0.3 tiM) but nearly abolished by a combination of the antagonists. Capsaicin and