What role the complement system in general, and C5a in particular play in hypersensitivity reactions in the lung is unknown. A review of the available studies indicates that C5a can mimic hypersensitivity reactions in the lung by virtue of its ability to cause cell infiltration and edema in the lung, cause of short lived airway hyperreactivity and cause bronchoconstriction. Its ability to cause contraction of isolated airways and in vivo bronchoconstriction in the guinea-pig is due to the release of histamine and arachidonate metabolites, mediator systems similar to those evoked by antigen-antibody reactions in the guinea-pig lung. To begin to determine if C5a generation with complement system activation was an important contributor to antigen-induced bronchoconstriction, the response to antigen was assessed in animals depleted of complement by cobra venom factor and unresponsive to C5a. Unexpectedly, these animals responded to antigen with a much greater bronchoconstriction than did animals with an intact complement system. This suggested that an intact complement system was somehow important in limiting allergic bronchoconstriction or conversely that allergic bronchoconstriction might be heightened when preceded by complement system activation. Thus, the data implicates C5a and/or complement system activation as a modulator of antigen-induced bronchoconstriction rather than directly contributing to the bronchoconstrictor component of hypersensitivity reactions in the lung.