1. Co-localization of SP and CGRP was observed in a dense intraepithelial and perivascular network of capsaicin-sensitive sensory nerves in the nasal mucosa of different species, including man. The morphological similarity in the distribution of these nerves among various experimental animals and man indicates that animal experimental data may be used for the understanding of sensory mechanisms in the human nasal mucosa. 2. Release of CGRP into the venous effluent of the nasal mucosa in parallel with vasodilatation was demonstrated in vivo upon antidromic stimulation of the maxillary division of the trigeminal nerve or local i.a. capsaicin injection. 3. Infusion of capsaicin induced concentration-dependent increase in arterial, venous and superficial blood flow as well as V in the pig nasal mucosa. Exogenous SP, CGRP and VIP displayed concentration-dependent, but partly separate, vasodilatory profiles in the nasal mucosa. SP was more potent regarding maximal blood flow increase, whereas the vasodilatation induced by CGRP infusion was more long-lasting on an equimolar basis. Although VIP caused an increase in ABF and VBF as well as V, the LDF signal (i.e. superficial blood flow) was decreased, possibly due to a stealing phenomenon. 4. Local i.a. capsaicin infusion induced a bilateral chlorisondamine-sensitive atropine-resistant vasodilatation. However, i.a. capsaicin in higher doses also induced a chlorisondamine-resistant vasodilatation in the superficial vascular compartment of the nasal mucosa, presumably via the release of sensory neuropeptides. Thus, the vasodilatory effect of capsaicin may be due to a complex interaction of local effects on the sensory nerve terminals close to blood vessels in the nasal mucosa and a main parasympathetic central reflex. 5. Capsaicin, but not nicotine, induced a concentration dependent increase in irritation or pain upon local application to the human nasal mucosa. Since both agents evoked secretion, this indicates that capsaicin and nicotine activate different populations of sensory neurons. Local application onto the nasal mucosa of capsaicin and nicotine as well as metacholine induced a concentration dependent muscarinic antagonist sensitive increase in the secretory response. The capsaicin or nicotine-induced secretion was bilateral and could be markedly reduced by combined pretreatment with a local anaesthetic and a vasoconstrictor. Our findings suggest that the secretory effect of capsaicin and nicotine in the human nasal mucosa is mediated via a central parasympathetic reflex arc with a final muscarinic receptor mechanism. No clear-cut contribution seemed to be exerted by locally released tachykinins and CGRP as direct trigger substances for the secretory response to capsaicin.(ABSTRACT TRUNCATED AT 400 WORDS)