The release kinetics of histamine and leukotrienes C4 (LTC4) and B4 (LTB4) were investigated in nasal secretions of 10 patients with hay fever after antigen challenge. High levels of biologically active histamine were found in nasal washes from asymptomatic allergic and normal subjects. With repeated lavages, the amount of histamine recovered dropped markedly. Grass pollen challenge was followed by a significant (p less than 0.05) dose-dependent and time-limited (5 min) increase in histamine level in 7 of 10 patients; these values, however, were lower than those found in basal conditions. In 8 of 10 patients with hay fever, antigen challenge induced a significant (p less than 0.05) dose-dependent increase in LTC4 level, which persisted for 30 min. The LTC4 generation was well correlated with the appearance of allergic symptoms; LTB4 production was found in 2 patients only. A different pattern of symptoms was observed after in vivo nasal stimulation with histamine and LTC4. Histamine caused sneezing, itching, rhinorrhea, and nasal obstruction; conversely, the main symptom induced by LTC4 was a more pronounced and longer lasting nasal obstruction.