This article reviews the contribution of cell-mediated inflammatory responses to the immediate immunoglobulin E-dependent allergic reaction. Apparently eosinophils play an important part in the pathogenesis of allergic reactions. Some new H1 antihistamines may also have non-H1-mediated antiinflammatory properties. In two double-blind, placebo-controlled, crossover studies of allergic and normal subjects, we showed that oral cetirizine, at dosages of 10 and 20 mg/day, significantly inhibited wheal-and-erythema reactions induced by grass pollen, 48/80, histamine, platelet-activating factor acether, and N-formyl-methionyl-leucyl-phenylalanine. In the first study, cutaneous eosinophil migration was significantly inhibited by cetirizine at pollen and 48/80 skin test sites (61%, p less than 0.01, and 53%, p less than 0.01, respectively), although no change was observed at histamine skin test sites. Inhibition of neutrophil accumulation was also observed at pollen and 48/80 sites (41%, p less than 0.1, and 31%, p less than 0.1, respectively). Monocyte accumulation was not affected by cetirizine. In the second study, cetirizine suppressed the eosinophil influx induced by pollen, platelet-activating factor, 400 ng, and platelet-activating factor, 40 ng (63%, p less than 0.001; 58.5%, p less than 0.001; and 57.8%, p less than 0.01, respectively). This inhibition was effective 2 hours after challenge and persisted through hours 4, 8, and 24. N-Formyl-methionyl-leucyl-phenylalanine induced a weak eosinophil accumulation that was inhibited by cetirizine.