The effects of carbonic anhydrase inhibition on the responsiveness to CO2 of pressure-sensitive laryngeal receptors were examined in anaesthetised, paralysed cats. Laryngeal CO2-sensitive receptors from the superior laryngeal nerve were selected by their responsiveness to intralaryngeal pressure and to perfusion of solution equilibrated with 9 % CO2. The carbonic anhydrase inhibitor, methazolamide, when given intralaryngeally at 10-4 M, diminished or abolished the responses to the CO2-equilibrated solution in four of six pressure-sensitive receptors. Histochemical staining for carbonic anhydrase activity showed that the larynges perfused with methazolamide had diminished carbonic anhydrase activity, especially on the superficial layers of surface epithelium. Compared to untreated controls, when given intravenously (50 mg kg-1) methazolamide diminished or abolished the responses to CO2 of five of the six fibres studied. Histochemical staining of these larynges showed no carbonic anhydrase reactivity at the sites of laryngeal receptors. These results suggest that the responses to CO2 of laryngeal pressure-sensitive receptors are dependent on the presence of carbonic anhydrase. Inhibition of laryngeal receptor carbonic anhydrase activity by methazolamide is more reliably achieved by systemic rather than by luminal administration. Experimental Physiology (2001) 86.5, 641-649.