The action of adenosine on adrenergic neuroeffector transmission was studied in the rabbit kidney in vitro and in situ, in the canine subcutaneous adipose tissue in situ and in the guinea pig vas deferens in vitro. In the kidney, adenosine (0.1-10 muM) caused a concentration-dependent increase in vascular resistance and in vasoconstrictor responses to nerve stimulation and administered noradrenaline. In the adipose tissue, adenosine also increased the vaso-constrictor responses but it decreased vascular resistance. In all three tissues studied adenosine significantly and reversibly depressed noradrenaline release evoked by nerve stimulation in a concentration-dependent manner. This effect of adenosine was not altered by phenoxybenzamine which blocked all vasoconstrictor responses and diminished the rise in vascular resistance by adenosine in the kidney. It is concluded that adenosine affects adrenergic neuroeffector transmission by two discrete mechanisms, prejunctional inhibition and postjunctional enhancement.