1. The overflow of dopamine and noradrenaline (NA) from the main trunk of the dog mesenteric artery and its proximal branches during prolonged depolarization (120 min) by K+ (52 mM) was quantified by high performance liquid chromatography with electrochemical detection. 2. K+-induced depolarization resulted in release of both dopamine and NA. The amount of NA released from both blood vessels declined progressively throughout the experiment. In the main trunk the same pattern of release was observed for dopamine, whereas in the proximal branches the overflow of dopamine increased throughout the experiment. 3. The addition of phentolamine (0.2 microM) to the perifusion fluid increased the overflow of both amines. In the presence of sulpiride (1 microM) the overflow of dopamine and NA was found to be increased in the proximal branches, but not in the main trunk. The addition of phentolamine to sulpiride caused a further increase in amine overflow in proximal branches, but not in the main trunk. 4. The addition of alpha-methyl-p-tyrosine (50 microM) to the perifusion fluid caused a decrease in the amounts of dopamine and NA released from both preparations. In alpha-methyl-p-tyrosine-treated preparations phentolamine increased amine overflow to the same extent as in experiments without tyrosine hydroxylase inhibition. The increasing effect of sulpiride on the overflow of dopamine and NA from the proximal branches was completely abolished after alpha-methyl-p-tyrosine. 5. The results presented suggest that in the proximal branches of the dog mesenteric artery, dopamine beta-hydroxylase represents a rate limiting step in the synthesis of NA; dopamine, through activation of prejunctional dopamine receptors acts like a prejunctional co-transmitter in the control of transmitter release, but only newly-synthesized dopamine appears to be responsible for this effect.