Objective. To analyze the concentration and distribution of the MCT (tryptase-positive, chymasenegative) and MC,, (tryptase-positive, chymasepositive) types of mast cell in cutaneous lesions of scleroderma.Methods. Biopsy specimens were obtained from skin lesions in 24 patients with scleroderma, and subjected to double immunohistochemical analysis using mouse monoclonal anti-tryptase and anti-chymase antibodies.Results. Dermal mast cell concentrations were below the normal range in 12 of the specimens, most of which were obtained between 1 and 4 years after disease onset. All other specimens contained normal concentrations of mast cells. MCT cells were present in 12 specimens and comprised between 8% and 100% of the total mast cells. Extracellular tissue deposits of tryptasepositive andor chymase-positive granular material were Two types of human mast cells have been recognized, based on their differential content of neutral proteases (1,2). The MCT cell contains tryptase (mean 10 pg/cell) but little, if any, chymase (CO.04 pg/cell); the MCTc cell contains both tryptase (mean 35 pg/cell) and chymase (mean 4.5 pg/cell). In addition, a cathepsin G-like proteinase and carboxypeptidase have recently been shown to be present in MCTc cells, but not MCT cells (3,4). Ultrastructural differences between these two types of mast cells have been described (5,6), and indirect evidence suggests that T lymphocyte factors are involved in the normal differentiation of MCT, but not MCTc, cells (7). In normal adult human tissues, MCTc cells predominate in the skin and the gastrointestinal submucosa, while MCT cells are the predominant type of mast cell in the gastrointestinal mucosa and alveolar walls of the lung (8).Mast cell activation is central to the pathogenesis of immediate-type hypersensitivity reactions. In addition, evidence for involvement of mast cells in fibrotic disorders is emerging, based on reports of increased numbers of mast cells in the skin during the active or inflammatory phase of scleroderma (9-1 l), in fibrotic lung disorders (12-14), and in keloids (15,16).