The occurrence of neurogenic inflammation as indicated by Evans blue extravasation was studied in various organs of the guinea-pig. Electrical stimulation of the trigeminal nerve caused Evans blue extravasation due to increased vascular permeability in the nasal mucosa and gingiva. Vagal stimulation induced extravasation in the epiglottis, larynx, trachea, bronchial tree and esophagus. Splanchnic stimulation induced Evans blue extravasation in the gall bladder, bile ducts and superior mesenteric artery. Stimulation of the inferior mesenteric ganglion caused a marked extravasation in the upper and middle part of both ureters, while pelvic activation induced a reaction in the lower ureter, urinary bladder, urethra and vagina. I.v. substance P (SP) (3 nmol X kg11) or capsaicin (1 mumol X kg-1) both induced extravasation in many tissues including those in which nerve stimulation produced a response. The extravasation responses to SP, capsaicin or nerve stimulation all had similar border-line zones, such as esophagus to stomach, bile ducts to duodenum, rectum to anal mucosa, pulmonary artery to heart and vagina to uterus. Quantitative determinations showed especially large permeability effects in the trachea, umbilical ligament and ureter. The permeability effect of capsaicin and nerve stimulation was abolished in capsaicin-pretreated animals, while the response to SP was still present. Capsaicin pretreatment caused an almost total loss of SP in several visceral organs including the respiratory and urinary tracts. The SP content in these tissues was correlated (r = 0.97) to the Evans blue extravasation following nerve stimulation or i.v. capsaicin. SP and capsaicin caused contractions in vitro of the esophagus, ureter, urinary bladder, trachea and gall bladder. The capsaicin-induced contraction of the trachea was resistant to tetrodotoxin pretreatment. The non-cholinergic, non-adrenergic contraction of the urinary bladder upon field stimulation was still present in capsaicin-pretreated animals. In conclusion, neurogenic inflammation occurs in several organs with a highly region-specific distribution, which is accompanied by the presence of capsaicin-sensitive SP neurons. Both parasympathetic and sympathetic pathways contain capsaicin-sensitive afferent fibres which mediate an increase in vascular permeability most likely by releasing SP. In addition, both capsaicin and SP cause smooth muscle contraction in several visceral organs.