1. The rebreathing and steady-state methods for assessing the response to inhaled carbon dioxide were compared in six normal subjects under control conditions and during metabolic acidosis and alkalosis.
2. The slopes of the CO2 response lines obtained with the two methods under control conditions were not significantly different.
3. Metabolic acidosis and alkalosis produced a significant change in the intercept of the response line when this was assessed with the steady-state technique. The slope of the response lines did not change significantly in alkalosis but there was probably a small increase during acidosis.
4. Using the rebreathing technique there was no significant change in intercept in acidosis and alkalosis, but the slope varied significantly from control values.
5. It is concluded that the two methods of assessing the respiratory response to inhaled CO2 are comparable under normal acid-base conditions. This similarity does not hold in metabolic changes of the acid-base state.