The anticoagulant activity of proteoglycans released from human lung mast cells was evaluated. Human lung mast cells were mechanically and enzymatically dissociated from normally appearing human lung fragments obtained during surgery for carcinoma and enriched by velocity gradient sedimentation. Mast cells ((1.00±0.31)×10(7)) were obtained with a purity of 20.1±3.3%. Isolated human lung mast cells, which were passive-sensitized with high IgE serum from an allergic patient and challenged with rabbit anti-human IgE or stimulated by calcium ionophore A23187, released proteoglycans which stained metachromatically with Azure A, as well as histamine. Both anti-thrombin activity (33.8±5.8%) and anti-Factor Xa activity (28.1%) were detected in proteoglycans released from human lung mast cells by the amidolytic method using chromogenic substrate S-2238 and S-2222, respectively. A significant correlation between anti-thrombin activity and the metachromatic change with Azure A was found. The metachromatic materials with anticoagulant activity were identified to be heparin by the criteria that they were resistant to degradation by chondroitin ABC lyase and chondroitin AC lyase, completely degraded by heparinase and inhibited by Polybrene. These data suggest that heparin proteoglycan released from human lung mast cells in an IgE mediated hyper-sensitivity reaction may prevent deposition of fibrin and play an important role at inflammatory lesions.