In contrast to the slow accumulation of fluid, plasma proteins and neutrophils observed after intrapleural injection of carrageenan, a second type of response is observed with mast cell degranulating agents, e.g. anti-IgE, compound 48/80, and dextran sulfate. In this response, there is rapid protein and fluid accumulation, which is generally correlated with the extent of histamine release, and at later stages neutrophil accumulation. Fluid and protein but not neutrophil accumulation is blocked by treatment with antihistamines. The response to destran T10 fits neither of these two categories. A rapid accumulation of protein- and cell-free transudate is associated with partial mast cell degranulation. This response is not blocked by pretreatment with antihistamines. Further, the extent of fluid accumulation is the pleural cavities of normal and mast cell-deficient mice (WBB6 F1/J-W.Wv) is the same. Thus, the response to dextran T10 is probably an osmotic effect rather than true inflammatory response to mast cell degranulation. The effects of dextran sulfate appeared to be a consequence of both osmosis (fluid accumulation) and response to release of mediators (protein and cell accumulation).