In order to identify possible functional differences between mast cells obtained from the skin of lichen planus (LP) patients and healthy donors, biopsies from lesional skin of 11 lichen planus patients and from normal skin of 7 healthy donors were sampled. Mast cells were obtained from the skin using an enzymatic dispersion technique. The cells were challenged in vitro with substance P (SP), tumor necrosis factor alpha (TNF-alpha) and anti-IgE. Their reactivity was estimated on the basis of histamine release. LP skin mast cells and healthy skin mast cells showed similar sensitivity to stimulation with TNF-alpha at a concentration of 10(-7) M (15.2% histamine release, as a proportion of total cellular content vs 15.9%) and to stimulation with anti-IgE at a dilution of 1:100) (38.8% vs 37.0%). Spontaneous histamine release was also very similar in both the populations of mast cells (10.2% vs 12.7%, respectively). However, LP skin mast cells showed significantly higher (P < 0.01) sensitivity towards stimulation with SP at a concentration of 10(-4) M than healthy skin mast cells (15.9% histamine release vs 7.0%). This finding could suggest that neurogenic inflammatory mechanisms contribute to the pathogenesis of LP.