The inhibitory effects of CO2 on slowly adapting pulmonary stretch receptors (SARs) were studied before and after administration of acetazolamide, a carbonic anhydrase inhibitor, or nifedipine, a calcium channel blocker, in anesthetized, artificially ventilated rabbits after vagus nerve section. CO2 inhalation (maximal tracheal CO2 concentration ranging from 7.2% to 9.5%) for approximately 60 sec decreased the receptor activity during both inflation and deflation. The magnitude of decreased receptor activity during deflation became more pronounced than that seen during inflation. Acetazolamide treatment (20 mg/kg) diminished the inhibitory responses of slowly adapting pulmonary stretch receptors to CO2 inhalation, which were not significantly influenced by pretreatment with nifedipine (1 mg/kg). Furthermore, CO2 inhalation before and after vagal denervation had no effect on total lung resistance and dynamic lung compliance. In another series of experiments, the staining to determine the presence of carbonic anhydrase enzymatic reaction was not found in the smooth muscle of either extrapulmonary or intrapulmonary bronchi. These results suggest that CO2-induced inhibition of slowly adapting pulmonary stretch receptors is not related to the change in bronchomotor tone.