AIM: To investigate the ability of natural chymase inhibitors to modulate histamine release from human mast cells. METHODS: Enzymatically dispersed cells from human lung, tonsil, and skin were challenged with anti-IgE or calcium ionphore A23187 in the absence or presence of the natural chymase inhibitors secretory leukocyte pro- tease inhibitor (SLPI) and α1-antitrypsin, then histamine release was determined. RESULTS: IgE-dependent hista- mine release from lung, tonsil, and skin mast cells were inhibited by up to 70%, 61%, and 62%, respectively following incubation with α1-antitrypsin (5000 nmol/L).SLPI 5000 nmol/L was also able to inhibit anti-IgE- dependent histamine released from lung, tonsil and skin mast cells by up to approximately 72%, 67%, and 58%, respectively. While neither α1-antitrypsin nor SLPI by themselves altered histamine release from lung, tonsil and skin mast cells, they were able to inhibit calcium ionophore-induced histamine release from lung and tonsil mast cells. CONCLUSION: Both α1-antitrypsinand SLPIcould potently inhibit IgE-dependent and calcium ionophore- induced histamine release from dispersed human lung, tonsil, and skin mast cells in a concentration-dependent manner, which suggested that they were likely to play a protective role in mast cell associated diseases including allergy. AIM: To investigate the ability of natural chymase inhibitors to modulate histamine release from human mast cells. METHODS: Enzymatically dispersed cells from human lung, tonsil, and skin were challenged with anti-IgE or calcium ionphore A23187 in the absence or presence of the natural RESULTS: IgE-dependent hista- mine release from lung, tonsil, and skin mast cells were inhibited by up to 70%, 61% , and 62%, respectively following incubation with α1-antitrypsin (5000 nmol / L) .SLPI 5000 nmol / L was also able to inhibit anti-IgE-dependent histamine released from lung, tonsil and skin mast cells by up to approximately 72% , 67%, and 58%, respectively. While neither α1-antitrypsin nor SLPI by themselves altered histamine release from lung, tonsil and skin mast cells, they were able to inhibit calcium ionophore-induced histamine release from lung and tonsil mast cells. CONCLUSION: Both α1-antitrypsin and SLPIcould potently inhibit IgE-dependent and calcium ionophore-induced histamine release from dispersed human lung, tonsil, and skin mast cells in a concentration-dependent manner, which suggested that they were likely to play a protective role in mast cell associated diseases including allergy.