Nitric oxide, synthesized from the guanidino group of L-arginine by nitric oxide synthase, has an important role in pathophysiological changes associated with anaphylaxis. Nitric oxide production due to activation of constitutive nitric oxide synthase is detected using a nitric oxide-selective electrode in anaphylactic rabbits in vivo. A nitric oxide synthase inhibitor attenuates hypotension and hemoconcentration and decreases venous return but does not improve cardiac depression. Nitric oxide functionally antagonizes the effects of vasoconstrictors released by anaphylaxis in vitro. In animals pretreated with a nitric oxide synthase inhibitor, the cardiac output falls significantly, although venous return is increased. Pulmonary resistance is significantly increased with a nitric oxide synthase inhibitor, and L-arginine attenuates the bronchospasm. These findings suggest that production of nitric oxide may reduce the pathophysiologic changes, except for vasodilatation, associated with anaphylaxis.