The involvement of neurokinin NK1 receptors in cigarette-induced adhesion of neutrophils and eosinophils to venules of the airway mucosa was investigated. Rats were pretreated with the NK1 receptor antagonist CP-99,994 (4 mg/kg IV), its vehicle, or its inactive enantiomer CP-100,263 before exposure to cigarette smoke. Adherent neutrophils and eosinophils were stained histochemically for endogenous peroxidase activity and were counted in tracheal whole mounts. Plasma leakage was quantified be stereological measurements of the extravasation of Monastral blue. Cigarette smoke induced the adhesion of 104 + 17 neutrophils and 10.4 +/- 1.7 eosinophils per square millimeter of mucosa. CP-99,994 reduced neutrophil and eosinophil adhesion by 66 and 61%, respectively, and reduced plasma extravasation by 61% (p < .05), but CP-100,263 had no significant effect. The inhibitory effects of CP-99,994 appeared to be specific because CP-99,994 had no effect on neutrophil and eosinophil adhesion, or on plasma extravasation induced by platelet activating factor, an inflammatory stimulus acting independently of NK1 receptors. These results suggest that NK1 receptors are involved in cigarette smoke-induced adhesion of neutrophils and eosinophils to the endothelium of venules in the rat tracheal mucosa.