Lungs from rabbits sensitized to ovalbumin or bovine γ-globulin were isolated and perfused with autologous blood. The response to antigen challenge via the perfusate was immunologically specific and characterized by a marked increase in perfusion resistance, a moderate increase in airway resistance and a small decrease in lung compliance. The response could also be elicited by specific antigen challenge in lungs from sensitized rabbits perfused with blood from normal rabbits and in lungs from normal rabbits perfused with blood or plasma from sensitized rabbits. The magnitude of the response was greater when blood or plasma from sensitized animals was used as the perfusate. Therefore, blood and/or plasma factors appear to be the major contributors to the response.