Psoriatic plaques contain an increased number of mast cells. Both the histamine concentration and release are increased in lesional skin but the underlying mechanisms are unclear. One hypothesis is that neuropeptides transmitted from thin sensory cutaneous nerves continuously stimulate mast cell release of histamine. The aim of this study was to test this hypothesis by examining if topical anaesthesia of these nerves inhibits histamine release in psoriatic skin. The concentration of histamine was measured in microdialysates obtained from lesional and non-lesional skin before and during topical anaesthesia. Concomitantly skin blood flow was measured with scanning laser Doppler (perfusion) and/or 133Xe clearance (flow) techniques in the microdialysis area. The histamine concentrations (mean +/- SEM) were 34 +/- 4 (n = 21), 14 +/- 1.5 (n = 18) (P < 0. 001) and 2.8 +/- 1 nmol/L (n = 10) in lesional and non-lesional skin and plasma, respectively. After anaesthesia of the microdialysis areas the histamine concentration in psoriatic skin increased to 44 +/- 4 nmol/L (n = 19, P < 0.05), but remained unaltered in uninvolved skin. In anaesthetized lesional skin the perfusion decreased from 3.7 +/- 0.2 to 2.5 +/- 0.3 V and blood flow decreased from 14 +/- 5 to 9 +/- 1 mL/min per 100 g (P < 0.001, n = 10). The calculated release of dermal histamine in involved skin (198 +/- 30 pmol/min per 100 g, n = 10) remained unchanged after local anaesthesia. The results indicate that neurogenic activation of mast cells is of minor importance for continuous histamine release in psoriatic skin and that the vasodilatation in the psoriatic plaque is not mediated by histamine.