Mastocytosis represents a group of disorders characterized by the proliferation and accumulation of mast cells in tissue. The aim of the present study was to examine whether the interstitial histamine concentration in the skin is increased in mastocytosis patients and whether it correlates with the number of mast cells, the amount of metabolite N-methyl-imidazole acetic acid in the urine and the tryptase in serum. In 7 mastocytosis patients on a standardized diet, the analysis of histamine was performed on microdialysates obtained from catheters positioned intracutaneously in involved and uninvolved skin. N-methyl-imidazole acetic acid in the urine was collected for 24 h. Biopsies for analyses of mast cells were taken from skin adjacent to the microdialysis catheters. The histamine concentrations were 42+/-14, 12+/-3 (P<0.05) and 8+/-2 nmol/l (mean+/-SEM, n=7) in skin eruptions, non-lesional skin and plasma respectively. Mean N-methyl-imidazole acetic acid in the urine (9.7+/-3.5 mmol/mol creatinine) and mean tryptase (124+/-54 microg/l) had increased in all patients. In the present study, no linear correlation was found between these parameters and interstitial histamine in lesional skin. This finding corresponds to the fact that the concentration of histamine metabolites and tryptase derives from the entire mast-cell population, while interstitial histamine in the dermis represents the local tissue concentration before metabolic transformation. The microdialysis of histamine in the skin of mastocytosis patients could be used as a tool to investigate the effects of dermal mast-cell histamine release in different kinds of treatment regimen.