As we continue to explore the biology of TGF-beta in the network of cells and mediators contributing to host defense, the mechanisms controlling whether the pro- or antiinflammatory effects of this peptide prevail will be unraveled. Understanding these basic mechanisms may offer new approaches for identifying agonists and/or antagonists and in which circumstances their use might be appropriate. The striking differences between local and systemic administration of this cytokine reaffirm that the functional consequences of any biologic mediator must be considered in context (9) and, furthermore, suggest avenues of therapeutic application (Table III). In summary, the central role of TGF-beta in normal and aberrant host defense has become indisputable.