1. We measured the ventilatory response to CO2 at two levels of arterial Po2 in twelve patients who suffered from chronic obstructive bronchitis. We also determined the lumbar cerebrospinal fluid bicarbonate in ten of these patients.
2. The CO2 response was depressed in nine patients who suffered from hypoxia and CO2 retention when breathing air. The hypoxic drive to breathing was normal in six cases, increased in one and absent in two cases who had severe chronic hypoxia and secondary polycythaemia.
3. The slope of the acute on chronic whole body CO2 titration line expressed in terms of arterial H+ and arterial Pco2 was the same in the hypercapnic patients as in normal men. This relationship allows predictions of the duration of hypercapnia in clinical practice.
4. Increased buffering in cerebrospinal fluid does not account for the depressed ventilatory response to CO2 in these patients.
5. By calculating the probable rise in jugular venous Pco2 which will follow correction of chronic hypoxia in these patients, we conclude that the administration of oxygen will remove a peripheral chemoreceptor stimulus to breathing but increase the central stimulus by a rise in cerebrospinal fluid acidity.