The effects of lidocaine on beta-adrenergic receptor binding and the yield of epinephrine-stimulated cAMP at different pH were measured by radioligand binding assay and radioimmunoassay. The results showed that the binding of H-DHA to the receptor and yield of epinephrine-stimulated cAMP increased with increasing pH (P < 0.001) and lidocaine inhibitory potency also increased with increasing pH (P < 0.001); The results indicate that the response to beta-agonists would increase with pH during cardiopulmonary resuscitation when lidocaine is not present, but it would not increase with pH when lidocaine is present, suggesting that lidocaine may inhibit binding of beta-agonists to receptor by changing lipid fluidity of cell membrane with increasing pH.