Slow-reacting substance of anaphylaxis (composed of leukotrienes C, D, and E) is released in vitro by the interaction of antigen and IgE antibody on human mast cells and basophils. When we challenged ragweed-sensitive patients intranasally with pollen grains, their clinical response was significantly correlated with the release of the peptide leukotrienes (P less than 0.001). Nonallergic subjects had neither symptoms nor leukotriene release. The leukotrienes were released in a dose-dependent fashion, with a peak mean level of 827 +/- 234 pg per 0.1 ml of a 10-ml nasal wash. High-performance liquid chromatography revealed the presence of leukotrienes C, D, and E, suggesting that nasal cells or fluids had the ability to degrade leukotriene C enzymatically. The in vivo release of these potent inflammatory mediators after exposure to pollen suggests that leukotrienes may have an important role in human allergic reactions.