To evaluate the relationship between atmospheric nitrogen dioxide exposure and the development of allergic diseases, the effects of nitrite as a chemical product of inhaled nitrogen dioxide on mast cell functions were investigated. We have studied nitrite-induced histamine release from two functionally distinct mast cell populations, namely peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC) of Nippostrongylus brasiliensis-infected rats. High concentrations of nitrite alone (10, 20, and 50 mM) induced histamine release from IMMC, but not from PMC. Moreover, histamine release from PMC and IMMC stimulated with sensitizing antigen was significantly enhanced by pretreatment with 50 mM nitrite or nitrate. No differences in histamine release from nitrite-treated and control PMC were seen below 1 mM. To investigate the effect of nitrite on tumor cell cytotoxic activity, PMC were incubated with various concentrations of nitrite. Pretreatment with 5 and 50 mM nitrite markedly depressed tumor necrosis factor (TNF)-alpha-dependent natural cytotoxicity of PMC for the tumor target WEHI-164. Thus, high concentrations of nitrite enhanced mast cell histamine release, but depressed TNF-alpha-dependent cytotoxicity. However, low concentrations of nitrite (< 1 mM) that would normally be produced by short-term atmospheric exposure to nitrogen dioxide may have no significant effects on mast cell functions.