The effect of exogenous dopamine on canine tracheal smooth muscle has been studied in-vitro. Dopamine at concentrations over 10(-5)M induced contractions of tracheal muscle strips and repeated exposures resulted in desensitization (tachyphylaxis) of the muscle. The sensitivity of the response varied dramatically among muscle strips. At lower concentrations, dopamine caused neither muscle relaxation nor inhibition of contractions evoked by 10(-6)M acetylcholine. Both a dopaminergic antagonist, haloperidol (10(-5) and 10(-4)M), and an alpha-adrenoceptor antagonist, phentolamine (10(-7) to 10(-5)M), attenuated the contraction to 10(-3)M dopamine. The beta-adrenoceptor antagonist, propranolol (10(-8) to 10(-6)M), enhanced the contraction. However, the contraction could only be abolished by phentolamine at 10(-4) M. Thus, in canine tracheal smooth muscle, the contractile response to dopamine is predominantly through the activity of alpha-adrenoceptors and the role of dopaminergic receptors is vague. It is suggested that the weakness of the dopamine-induced contraction results from an antagonism between alpha- and beta-adrenoceptor effects and the dopamine tachyphylaxis may reflect a gradually decreased activation of the alpha-adrenoceptor mechanism in comparison with the beta-adrenoceptor mechanism.