The overflows of noradrenaline (NA) and neuropeptide Y like immunoreactivity (NPYLI) and vascular responses upon sympathetic nerve stimulation were analysed in the nasal mucosa of pentobarbital anaesthetized pigs. In controls, a frequency‐dependent increase in NA overflow was observed whereas detectable release of NPY‐LI occurred only at 6.9 Hz. Parallel decreases in blood flow in the sphenopalatine artery and vein and in nasal mucosa volume (reflecting blood volume in the venous sinusoids) were observed. The laser Doppler flowmeter signal (reflecting superficial blood flow) increased upon low and decreased upon high frequency stimulation. Twenty‐four hours after reserpine pretreatment and preganglionic decentralization, the NA overflow was abolished while a frequency‐dependent release of NPY‐LI occurred. Forty, 60 and 80% of the vasoconstrictor responses then remained upon stimulation with a single impulse, 0.59 and 6.9 Hz, respectively. Both the vasoconstriction and NPY‐LI overflow, however, were subjected to fatigue upon repeated stimulation. In reserpinized animals release of NPY‐LI and vasoconstrictor responses were larger upon stimulation with irregular bursts at 0.59 Hz compared to effects seen at stimulation with continuous impulses. Pre‐treatment with the a‐adrenoceptor antagonist phenoxybenzamine or the monoamine reuptake inhibitor, desipramine, enhanced NA overflow by 2–3 and 1.5 times at 0.59 and 6.9 Hz, respectively. Phenoxybenzamine significantly reduced the nerve‐evoked vascular responses while the release of NPY‐LI at 6.9 Hz was increased. Desipramine increased the functional responses but reduced the NPY‐LI overflow. During tachyphylaxis to the vasoconstrictor effects of the stable adenosine 5′‐triphosphate (ATP) analogue α‐β‐methylene ATP (mATP) in controls, the vasoconstrictor responses as well as the NA and NPY‐LI overflow to nerve stimulation were unmodified. In reserpinized animals, however, the vascular responses and the overflow of NPY‐LI were reduced after mATP tachyphylaxis.These data show that both NA and NPY are released upon sympathetic nerve stimulation in the nasal mucosain vivoand this release seems to be regulated via prejunctional a‐adrenoceptors. The lack of effect of mATP tachyphylaxis under control conditions makes it less likely that ATP serves as a major mediator of the larg