To further define the role of histamine in the nasal mucosa, we studied the possible effect of histamine provocation on the generation of prostanoids and leukotrienes, and on the induction of hyperresponsiveness to methacholine. In separate experiments, we performed nasal challenges with histamine and measured by gas chromatography negative ion mass spectrometry and by radioimmunoassay after high-performance liquid chromatography the levels of prostanoids and leukotrienes, respectively, in recovered nasal lavages 10 min after challenge. Hyperresponsiveness to methacholine was tested in both nostrils 24 h after unilateral provocation with histamine. Our data suggest that histamine induced an immediate symptomatic response, but neither led to the generation of prostaglandins or leukotrienes nor induced hyperresponsiveness to methacholine. These results differ from those achieved after antigen stimulation and emphasize the importance of mediators in addition to histamine in the allergic reaction.