Abstract Since much of the data on heterogeneity in the rodent systems are based on differential effects of drugs, we compared responses of human lung mast cell and intestinal mucosal mast cell populations to agents that have revealed mast cell heterogeneity in rat models, as well as to other agents that are effective in both rat peritoneal and intestinal mast cell preparations. Disodium cromoglycate and theophylline inhibit histamine release (HR) from rat peritoneal, but not intestinal, mast cells. We found disodium cromoglycate (10 −4 to 10 −8 mol/L) to be ineffective in both human lung and human intestinal mast cell preparations, whereas theophylline (10 −3 to 10 −6 mol/L) inhibited both lung and intestinal mast cell HR. Quercetin (10 −4 to 10 −8 mol/L) and doxantrazole (3 × 10 −4 to 10 −7 mol/L), which inhibit both rat mast cell types, also inhibit HR in both human mast cell preparations. We also examined the actions of indomethacin and exogenous arachidonic acid and found that neither the lung nor the intestinal mast cells demonstrated the enhancement of HR stimulated by these agents in the basophil. In summary, we have found no pharmacologic differences between the human lung and intestinal mucosal mast cell such as exist in the rodent models. This underscores the limitations of applying the data from animal mast cells to the human mast cells, and at the same time demonstrates that human basophils and mast cells are different.