1 In in vitro experiments adenosine 5'-triphosphate (ATP) and adenosine were found to exert different effects on the guinea-pig isolated trachea depending on whether the trachea had previously been contracted with acetylcholine (ACh) (6.6 x 10(-6) M) or was at resting tone. 2 ATP and adenosine (10(-5) and 10(-3) M) were equipotent in relaxing the precontracted guinea-pig trachea, since concentrations of 1.09 +/- 0.35 and 0.39 +/- 0.16 mM respectively reduced by 25% the ACh-induced contraction. 3 ATP and adenosine (10(-5) and 10(-4) M) caused a moderate contraction of the guinea-pi trachea under resting tone. This effect was antagonized by inhibitors of cyclo-oxygenase (indomethacin 10(-6) M, aspirin 0.3 x 10(-3) M and 3 x 10(-3) M) and of thromboxane synthetase (nictindole 10(-7) M, imidazole 5 x 10(-5) M), which suggests an indirect mechanism of action with release of arachidonic acid derivatives.