The largest rami caecales of the ileocolic artery, which is a branch of the mesenteric artery, were perfused at a constant rate of flow. Either vasoconstriction (as an increase in perfusion pressure) or the release of previously incorporated [3H]-noradrenaline was measured. Noradrenaline and ATP, but not carbachol, serotonin, adenosine, Arg-vasopressin and neuropeptide Y, caused marked vasoconstriction. When the sympathetic vasoconstrictor axons in the arterial wall were stimulated by electrical field pulses (either 5 pulses at 10 Hz or 100 pulses at 5 Hz; 0.3 ms pulse width, 200 mA current strength), the ensuing vasoconstriction was at best slightly reduced by phentolamine, prazosin and phenoxybenzamine. The response to 100 pulses, 5 Hz was even enhanced by phentolamine and yohimbine. All antagonists except yohimbine blocked the effect of exogenous noradrenaline. Prazosin did not change the effect of exogenous ATP. alpha,beta-Methylene-ATP (3-15 mumol/l) elicited transient vasoconstriction. Subsequently, responses to ATP as well as to electrical stimulation were reduced and recovered slowly. The response to noradrenaline was not changed. That part of the electrically induced vasoconstriction that remained after alpha,beta-methylene-ATP was almost abolished by phentolamine or prazosin. Pre-treatment of the animals with reserpine decreased but did not prevent the electrically evoked contraction of their arteries. The reserpine-resistant response was not changed by prazosin but was abolished by alpha,beta-methylene-ATP. The vasoconstriction elicited by electrical pulses was not affected by atropine or methysergide but was entirely blocked by tetrodotoxin, guanethidine or exposure to 6-hydroxydopamine. In arteries pre-incubated with [3H]-noradrenaline, electrical stimulation (100 pulses at 5 Hz) increased the outflow of tritium. The evoked overflow was blocked by tetrodotoxin, not changed by alpha,beta-methylene-ATP (9 mumol/l) or prazosin, and enhanced by phentolamine, phenoxybenzamine and yohimbine. We conclude that, in the branch of the mesenteric artery examined, both noradrenaline and ATP or a closely related compound transmit information from sympathetic neurones to smooth muscle. An alpha-adrenoceptor antagonist can reduce neurogenic vasoconstriction by blockade of post-junctional alpha-(probably alpha 1) receptors, reserpine by selective depletion of noradrenaline, and alpha,beta-methylene-ATP by desensitization of the post-junctional ATP (probably P2) receptor mechanism. Noradrenaline and ATP appear to be released from the same neurone. In addition, prejunctional alpha 2-adrenergic autoinhibition of transmitter release operates in the artery. alp