CO2 sensitivity in the airways and the general skin surface of the bullfrog under urethane anesthesia or without anesthesia was investigated. Pressure in the buccal cavity and blood pressure in the sciatic artery were measured with a differential or a strain gauge transducer. Air containing 2-14% CO2 was introduced into the regions as given below. The nose and the body surface regions were both separated from each other and independently exposed to CO2. The larynx-lungs, the buccal cavity-lungs, the naso-buccal cavity separated from the airways at the glottis, and the internal or external nares, respectively. By analyzing the CO2 sensitivity of the respective regions [nose and body surface], both the nasal mucosa and the skin surface were responsible for the respiratory inhibition by CO2. Sectioning both the olfactory and the trigeminal nerves abolished the CO2-induced inhibition mediated by the nasal mucosa and electrical stimulation of the proximal cut end of these nerves inhibited respiration. The existence of afferent reflex pathways from the nasal mucosa by these cranial nerves was suggested. Significance of this CO2-induced reflex was discussed.