Lesional (n= 15) and non-lesional (n= 10) skin of subjects with mastocytosis was analysed for the distribution and concentration of trypase positive, chymase negative mast cells (MCT) and tryptase positive, chymase positive mast cells (MCTC) cells and compared to normal skin (n= 23) and non-lesional skin of subjects with unexplained anaphylaxis or flushing episodes (n= 6). Skin biopsies were fixed in Carney's fluid and subjected to double immunohistochemical staining with biotinylated mouse monoclonal anti-chymase antibody followed by alkaline phosphatase-conjugated mouse monoclonal anti-tryptase antibody. MCTC cells were the only type of mast cells seen in all specimens analysed and in each case were more numerous in superficial compared to deep regions of dermis. The concentration (mean ± s.d.) of mast cells in the superficial dermis of mastocytosis lesions (40985 ± 21772 mast cells/mm3) was significantly increased over that in corresponding areas of non-lesional skin from subjects with mastocytosis (7178 ± 3607 mast cells/mm3), skin from subjects with idiopathic anaphylaxis or flushing episodes (6974 ± 3873 mast cells/mm3) and normal skin (7347 ± 2973 mast cells/mm3). The exclusive presence of MCTC cells in skin lesions of mastocytosis which are characterized by non-malignant hyperplasia of mast cells suggests involvement of local tissue factors in mast cell recruitment and differentiation.