The nasal antigen challenge model has proved useful in assessing the roles of inflammatory mediators in the clinical allergic response. Studies using this model have revealed that the acute allergic response is associated with increased concentrations of histamine, prostaglandin D2 (PGD2), leukotrienes, tryptase, and kinins, and with increased TAME-esterase activity. The effects of antihistamines on the clinical response and inhibition of mediator release have also been examined with this model. Premedication with terfenadine caused a marked reduction in sneezing as well as decreased histamine release, kinin levels, and TAME-esterase activity. Levels of PGD2 also decreased, although not significantly. Release of leukotriene C4 (LTC4) was not affected by this agent. Terfenadine also reduced vascular permeability as reflected in decreased albumin levels. In this model, cetirizine reduced sneezing, TAME-esterase activity, and albumin levels, whereas histamine release and PGD2 levels remained unaffected. Pretreatment with cetirizine resulted in significantly reduced levels of LTC4. Loratadine markedly, but not significantly, inhibited the sneezing response and reduced release of histamine, PGD2, and LTC4. Albumin and kinin levels were significantly diminished. The clinical significance of the inhibitory effects of antihistamines on mediator release has yet to be determined.