1. The nature of the transmitter mediating vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation was studied. 2. Prazosin (0.1 microM) abolished the response to exogenously applied phenylephrine (1 microM) but had no effect on constrictions of submucosal arterioles evoked by nerve stimulation (100 pulses at 10 Hz). 3. Vasoconstrictions and excitatory junction potentials elicited by nerve stimulation were potentiated by idazoxan (0.1 microM). 4. Following reserpine treatment, catecholamine fluorescence was absent in submucosal arterioles but nerve-evoked vasoconstrictions were unaltered. 5. Vasoconstrictions and excitatory junction potentials recorded in response to sympathetic nerve stimulation, as well as constrictions evoked by exogenously applied ATP (3 microM), were abolished by the P2-purinoceptor antagonist, suramin (100 microM). Suramin had no effect on the vasoconstriction in response to noradrenaline (3 microM), or the nicotinic excitatory postsynaptic potentials (e.p.s.ps) and noradrenergic inhibitory postsynaptic potentials (i.p.s.ps) recorded from submucosal neurones. 6. We conclude that postjunctional responses of submucosal arterioles following sympathetic nerve stimulation are mediated solely through the activation of P2X-purinoceptors by ATP or a related purine nucleotide. The function of neurally released noradrenaline is to act through prejunctional alpha 2-adrenoceptors to depress transmitter release.