Protective effect of alpha-human atrial natriuretic peptide (alpha-hANP) on pulmonary edema was investigated using an isolated perfused lung model. Infusion of alpha-hANP (1.7 to 22 ng/ml or 0.56 to 7.3 nM) prevented the edema induced in isolated lung from guinea pig by repeated treatment of 50 micrograms of arachidonic acid at 30 min intervals via the pulmonary artery. The antiedematic action of alpha-hANP was considered to be receptor mediated because the effective concentration was close to the Kd value of the binding of the ANP receptors in the lung homogenate.