The responses of ventilation and of medullary extracellular fluid (ECF) pH and PCO2, to an intravenous (i.v.) infusion of 50 mg/kg acetazolamide (an inhibitor of carbonic anhydrase), were measured in cats anaesthetized with chloralose and urethane, in which both bilateral vagotomy and carotid nerve section had been performed. After 2 h, it was observed that: acetazolamide caused an acidosis in medullary ECF which was still developing after 2 h, reflected by a progressive fall in pH (mean = 0.215 pH units in 2 h), while ECF PCO2 showed an insignificant rise of about 1 kPa; acetazolamide caused a considerable rise in ventilation, which largely developed in the first 15 min after drug infusion; the direction of the ECF acid-base responses in the first 15 min varied, whereas that of the ventilatory response did not. Furthermore, the time course of the former developed quite differently from the latter. It was therefore concluded that the observed changes in medullary ECF pH and PCO2 can not explain the large and fast ventilatory response of acetazolamide.