Antigen challenge in allergic subjects and in sensitized animals causes recruitment of neutrophils as well as eosinophils into the airways. In this study, we asked whether interleukin-8 (IL-8) is involved in the recruitment of neutrophils into the airways after antigen challenge. We administered ragweed antigen to an isolated, superfused tracheal segment of ragweed-sensitized dogs. Local tracheal instillation of the antigen caused an increase in IL-8 concentration and increases in both the number of recruited neutrophils and myeloperoxidase activity (one indicator of neutrophil activation in the recruited cells). The increase in IL-8 concentration was observed earlier than both the neutrophil recruitment and the increase in myeloperoxidase activity in the tracheal superfusate. Superfusate removed from the trachea 8 h after antigen challenge showed marked neutrophil chemotactic activity in a microchemotaxis chamber, and this activity was inhibited (mean, 75.6%) by a blocking antibody to dog IL-8. We conclude that ragweed antigen causes neutrophil recruitment into the airways at least in part because of IL-8 production.