The purpose of the present studies was to begin to test the hypothesis that the complement system is important for antigen-induced bronchoconstriction in the guinea pig. The effect of the complement-depleting agent cobra venom factor (CVF) on antigen-induced bronchoconstriction in guinea pigs passively sensitized with IgG or IgE antibody to ovalbumin was determined. Intravenous injection of CVF significantly reduced total hemolytic complement activity (CH50), caused a transient decrease in dynamic lung compliance, an increase in pulmonary resistance, and a decrease in circulating white blood cells with a sustained decrease in platelets. Antigen-induced bronchoconstriction was not inhibited in either IgG- or IgE-sensitized guinea pigs depleted of complement. Thus, a role for the complement system as a contributing factor in antigen-induced bronchoconstriction was not supported. On the contrary, our studies revealed an enhanced antigen-induced bronchoconstriction in guinea pigs depleted of complement with CVF. Our studies were then directed towards characterizing the enhanced response to begin to determine the mechanism responsible. The enhanced antigen-induced bronchoconstriction occurred in both IgG- and IgE-sensitized guinea pigs and was most apparent at lower antigen doses. The enhanced response still occurred in animals treated for 5 min with a dose of CVF (10 U) which caused no demonstrable decrease in CH50, a 30% level of conversion of C3, and a normal response to C5a. These data suggested that the enhanced response was not related to the level of C5a responsiveness of the animal. In addition, CVF-treated animals were normally responsive to various purported mediators of antigen-induced bronchoconstriction: histamine, leukotriene C4, platelet activating factor, the thrombox-ane-mimetic U-46,619, and prostaglandin F2α. The response to prostaglandin D2 was slightly enhanced. Thus, CVF treatment did not result in a generalized airway hyperreactivity. Since antigen-induced bronchoconstriction was not inhibited in animals depleted of complement, these studies suggest that an intact complement system is not necessary for this antigen-induced event. However, the enhanced antigen-induced bronchoconstriction seen after CVF treatment suggests that complement depletion and/or activation in vivo may be an important modulator or determinant of the severity of a subsequent antigen-induced bronchoconstriction.