The overall objective of this project is to further characterize the underlying mechanisms and significance of inflammatory cell responses in the sites of human allergic reactions. The overall approach will utilize techniques adapted by us that permit: 1) sequential measurements of mediator release and inflammatory cell responses in the skin reactions to pollen antigens; 2) sequential measurement of allergic serum chemotactic factors and other mediators after antigen inhalation challenge. Specific aims include determination: 1) Whether a single antigen challenge in the skin of sensitive subjects leads to a single burst or continued mediator release and how this relates to sequential inflammatory cell responses. 2) Whether qualitatively different mediator release patterns occur in immediate and delayed responses to intradermal or inhaled antigen and how this relates to clinical manifestations of the subjects. 3) The effects of the local allergic environment on subsequent mediator release and inflammatory cell function. 4) The source and biologic effects of neutrophil chemotactic activity we found to be increased during antigen-induced bronchospasm. 5) The effects of immunotherapy on such responses. Findings in this project may provide a basis for more effective treatment in human allergic diseases.